Myeloid Sarcomas Causing Unilateral Cranial Nerve Palsies in a Patient with Relapsed Acute Myeloblastic Leukemia.

Myeloid sarcomas (MS) are a rare manifestation of myeloid malignancies and can often be misdiagnosed, leading to a delay in treatment. The objective of this clinical case is to highlight the challenges of the clinical presentation and to emphasize the importance of this manifestation ensuring timely diagnosis and therapy. Here, we present a 43-year-old man who was diagnosed with acute myeloblastic leukemia (AML) after being evaluated for unintentional weight loss, subcutaneous nodules, thrombocytopenia, and anemia. The patient underwent chemotherapy with complete remission and presented 4 months later with dysphagia and cranial nerve palsies. Appropriate imaging and biopsy led to a diagnosis of myeloid sarcoma, and a decision was made to begin reinduction chemotherapy for AML achieving a second complete remission although his neurological deficits did not improve. Our case illustrates the protean presentation of myeloid sarcomas; clinicians should have a high suspicion for MS and remain vigilant when unexplained signs and symptoms arise in the background of a myeloid malignancy although challenges still remain when presentation is de novo. Advancements in understanding the pathophysiology of MS have been performed but remain not completely understood. High clinical suspicion, appropriate imaging, biopsy techniques, and expertise are paramount for timely diagnosis and treatment.

Venous Thromboembolism Is an Independent Predictor of Mortality Among Patients with Gastric Cancer.

BACKGROUND: Venous thromboembolism (VTE) is an independent predictor of death among patients with cancer. Patients with gastric cancer (GC) are at higher risk for VTE when compared to other solid tumors, and if one considers its prevalence, GC may be responsible for one of the highest incidences of cancer-associated thrombosis. The impact of VTE on mortality is not well defined among patients with GC. AIM: The aim of this study is to measure the impact of VTE as independent predictor of GC mortality. METHODS: Chart review of patients with GC treated in the Department of Oncology at John Stroger Hospital between the years of 2010 and 2015. VTE events were objectively confirmed with imaging in all cases. Active GC was defined as biopsy-proven metastatic disease or on active chemotherapy. Along with cancer-specific data, we abstracted risk assessments tools, non-GC-specific, validated for VTE and mortality prediction cancer, including the Khorana score (KRS), platelet lymphocyte ratio (PLR), and neutrophil lymphocyte ratio (NLR). Continuous variables are expressed by the median as appropriate according to normality. Categorical variables are expressed as percentages. SPSS version 22 was used and chi-square, Mann-Whitney U, Kaplan-Meier curve, and Cox proportional hazard with forward modeling were applied. RESULTS: We included 112 patients in the analysis. The patients were predominantly men (66%), 58-year-old, with adenocarcinoma (84%) and advanced disease (59%). The median follow-up was 21.3 months (IQR 8.9-42.4). Cumulative incidence of VTE at 1 year was 9%. The median time from diagnosis to VTE occurrence was 59 days (IQR 36 to 258). Patients with VTE had worse OS when compared to the non-VTE group (medians 11.87 vs 29.97 months, p = 0.02). Patients stratified as high risk by the PLR had worse OS (medians 22.6 vs 42.77 months, p = 0.02). There was no statistical difference in OS among patients stratified as high risk by the KRS (medians 23.7 vs 42.5, p = 0.16) and NLR (medians 24.1 vs 42.7 months, p = 0.21). In multivariate analysis, the independent predictors of mortality were VTE (hazard ratio (HR), 2.9; 95% CI, 1.4 to 6.6; p < 0.01), adenocarcinoma (HR, 3.1; 95% CI, 1.1 to 9.0; p = 0.03), advanced disease (HR, 2.8; 95% CI, 1.4 to 5.8; p < 0.01), and PLR (HR, 2.2; 95% CI, 1.3 to 3.8; p < 0.01). CONCLUSION: VTE is associated with worse survival among patients with GC along with adenocarcinoma, advanced disease, and PLR. Moreover, these findings were independent of other cancer- and treatment-specific variables. Although potentially predictive in other cancer types, NLR and KRS were not associated with worse survival in this cohort.

Performance of Current Thromboembolism Risk Assessment Tools in Patients With Gastric Cancer and Validity After First Treatment.

Patients with gastric cancer (GC) are at higher risk of thromboembolism when compared to other solid tumors. We aim to determine the predictive performance of current venous thromboembolism (VTE) predictive tools and their variability and validity after first treatment. Single institution cohort of GC-treated patients (2010*15). We abstracted predictive tools, validated for VTE prediction in patient with cancer; including the Khorana Score (KRS), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR). The primary outcome was CAT prediction. We included 112 patients who were predominantly men (66%), 58 (51-64)-year-olds, with adenocarcinoma (84%) and advanced disease (59%). The median follow-up was 21.3 months (9.5-42.6). The VTE occurrence was 12%. The median time from diagnosis to VTE occurrence was 59 days (36-258). In our cohort, performance status (PS; hazard ratio [HR], 8.02; 95% confidence interval [CI], 2.37-27.14; P < .01) was an independent predictor of VTE whereas KRS (univariate HR, 2.3; 95% CI, 0.7-7.4; P = .17), PLR (univariate HR, 0.8; 95% CI, 0.2-3.1; P = .8), and NLR (univariate HR, 0.8; 95% CI, 0.3-2.5; P = .8) at baseline were not associated with VTE risk. The posttreatment KRS was an independent predictor of VTE (HR, 3.69; 95% CI, 1.17-11.65; P = .25) along with PS (HR, 7.58; 95% CI, 2.27-25.33; P = .01). Posttreatment KRS appears as a valid tool to identify patients with GC at high risk of VTE after first cancer treatment.

Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer.

BACKGROUND: Venous thromboembolism (Wickham et al., 2012 [1]) is a leading cause of morbidity and mortality among patients with cancer; however, primary thromboprophylaxis is not routinely recommended. We performed a systematic review and meta-analysis of randomized control trials (RCTs) to measure the impact of primary VTE prevention and its effect on mortality among patients with lung cancer. METHODS: With assistance from a master librarian, we searched Ovid, Scopus, DARE, CINAHL, MEDLINE, EMBASE, EBM reviews-Cochrane database of systematic reviews, EBM reviews-ACP journal, and EBM Reviews-Databases for relevant studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included articles addressing the role of anticoagulation in patients with lung cancer for primary VTE prevention for outpatients. The clinical outcomes were VTE occurrence, all-cause mortality, major and clinically relevant non-major bleeding. The results are presented as odds ratio (OR) and data were analyzed using R and R META package (Version 0.8-2, Author: Guido Schwarzer). RESULTS: Eleven studies with 5107 patients were included for the final analysis. We found 50% lower VTE occurrence in the prophylaxis group with low molecular weight heparin (LMWH) (OR: 0.50; 95% Confidence Interval (CI): 0.38-0.66; I2: 0%) without an increased bleeding risk (OR: 2.03; 95% CI: 0.78-5.25; I2: 71.1%). We found a mortality benefit when we grouped all VTE prevention modalities [LMWH, Warfarin, unfractionated heparin (UFH)] (OR: 0.75; 95% CI: 0.58-0.96; I2: 18.4%), but no significant difference when LMWH (OR: 0.74; 95% CI: 0.49-1.11; I2: 56.9%) and warfarin were analyzed individually (OR: 0.75; 95% CI: 0.47-1.21; I2: 0%). We found higher odds of bleeding combining all treatment modalities (OR: 3.06; 95% CI: 1.64-5.72; I2: 64.4%) with the greatest occurrence in the warfarin group (OR: 5.42; 95% CI: 3.48-8.45; I2: 45.7%). CONCLUSION: Primary VTE prophylaxis with LMWH reduces the occurrence of VTE among ambulatory patients with lung cancer, without apparent increase in bleeding risk. There is a measurable mortality benefit of anticoagulation strategies that remains elusive when the analysis is restricted to a single agent.

Validation of a Patient-Completed Caprini Risk Score for Venous Thromboembolism Risk Assessment.

Introduction Individualized risk assessment for venous thromboembolism (VTE) using the Caprini risk score (CRS), coupled with targeted prophylaxis based on the score, is effective in reducing postoperative VTE. Critics contend that using this tool is time consuming for health care providers. We decided to create a patient-completed CRS and conducted a prospective study to compare the scores calculated by a patient with those calculated by a blinded physician for the same patient. Methods In phase 1, we interviewed patients in our deep vein thrombosis (DVT) support group who had a history of thrombosis and included their family members to determine areas of misunderstanding in the original CRS. We created a patient-completed form based on these interviews. In phase 2, we further optimized the questions after a CRS-trained, blinded physician scored 20 hospitalized patients during the pilot study. In the final (third) phase, we measured the agreement level between the new form filled out by the trained physicians and those filled out by the patients. The study was approved by our local institutional review board. Using PASS version 11, we determined that a sample size of 37 individuals achieves a power of 80%, to detect a 0.1 difference between the null hypothesis correlation of 0.5 and the alternative hypothesis correlation of 0.7 using a two-sided hypothesis test with a significance level of 0.05. We tabulated the individuals' answers and categorized the scores by using SPSS version 23 to estimate the kappa value, linear correlation, and the Bland-Altman test. A kappa value greater than 0.8 indicated an "almost perfect agreement." Results We tested the first patient-completed CRS version (phase 2) in a 20-patient pilot study. A poor agreement was observed with the body mass index (BMI) responses in multiple iterations, and so we excluded the BMI calculation from the final patient-completed CRS form. We recruited 42 patients with an average age of 55, mostly female (45%), who completed less than college education (62%) to fill out the updated CRS form (phase 3). An almost perfect agreement was found for both the individual questions and the overall score comparing physician and patient answers, resulting in a high correlation ( r = 0.95). In Bland-Altman, we did not find any trend for extreme values. Conclusion We created and validated a patient-completed CRS form that has an excellent agreement level with the physician-completed form. From the results, the physician only needs to calculate the BMI. The average time for a patient to complete the form was 5 minutes. The average time for the physician to finalize the score was approximately 6 minutes. Implementation studies are needed to assess the correlation of the aggregated score, derived from this form, with the occurrence of perioperative VTE.

Effect of 17á-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats

The objective of the present study was to evaluate the effect of 17á-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17á-estradiol at a dose of 30 æg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17á-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass

Effect of 17beta-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats.

The objective of the present study was to evaluate the effect of 17beta-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17beta-estradiol at a dose of 30 microg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17beta-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass.

[Animal models of osteoporosis]. / Modelos animais de osteoporose.

The authors review the literature regarding the animal models of osteoporosis in two main groups: The resorption-dominant models (oovariectomy, orchiectomy, limbs imobilization, calcium restriction and use of hormonies) and another group, the formation-deficit models (senil rats, SAM mouse, glucocorticoid administration or limbs imobilization.