Targeting CD33 for acute myeloid leukemia therapy

Abstract Background The aim of this study was to analyze the level of CD33 expression in patients with newly diagnosed AML and determine its correlation with clinical characteristics. Methods Samples were collected for analysis from AML patients at diagnosis. We evaluated the level of CD33 expression by flow cytometry analysis of bone marrow. Chi-square or t- tests were used to assess the association between the high and low CD33 expression groups. Survival curves were generated by the Kaplan-Meier and Cox regression model method. Results In this study we evaluated the level of CD33 expression in de novo patients diagnosed from November 2013 until January 2019. The mean value of 73.4% was used as the cutoff for the two groups. Statistical analysis revealed that 53 of the 86 (61.2%) AML patients were above the mean. Although there was no statistical significance between CD33 expression level and gene mutation, FLT3 mutation (P = 0.002) and NPM1 mutation (P = 0.001) were more likely to be seen in the high CD33 group. The overall survival (OS) was worse in the high CD33 group (39.0 m vs. 16.7 m, x2 = 13.06, P < 0.001). The Cox survival regression display that the CD33 is independent prognostic marker (HR =0.233,p = 0.008). Univariate analysis showed that the high expression of CD33 was an unfavorable prognostic factor. Of the 86 patients, CD33-high was closely related to the patients with normal karyotype (x2 = 4.891,P = 0.027), high white blood cell count (WBC, t = 2.804, P = 0.007), and a high ratio of primitive cells (t = 2.851, P = 0.005). Conclusions These findings provide a strong rationale for targeting CD33 in combination with chemotherapy, which can be considered a promising therapeutic strategy for AML.

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Targeting CD33 for Acute Myeloid Leukemia Therapy

10.21203/rs.3.rs-847355/v1 ◽

2021 ◽

Author(s):

Jing jing liu ◽

Jia Yin Tong ◽

Hai Ping Yang

Keyword(s):

De Novo ◽

Statistical Significance ◽

Normal Karyotype ◽

Mean Value ◽

High Ratio ◽

Categorical Variables ◽

Chi Square ◽

Npm1 Mutation ◽

Kaplan Meier ◽

The Mean

Abstract Objective The aim of this study was to analyze the level of CD33 expression in patients with newly diagnosed AML and determine its correlation with clinical characteristics. Methods: Samples were collected for analysis from AML patients at diagnosis. We evaluated the level of CD33 expression by flow cytometry analysis of bone marrow. Chi-square or t- tests were used to assess the association of categorical variables between the high and low CD33 expression groups. Spearman’s rho was applied when appropriate. Survival curves were generated by the Kaplan–Meier method. Results ① In this study we evaluated the level of CD33 expression in de novo patients diagnosed from November 2013 until January 2019. The mean value of 73.4% was used as the cutoff for the two groups. Statistical analysis revealed that 53 of the 86 (61.2%) AML patients were above the mean.② Although there was no statistical significance between CD33 expression level and gene mutation, FLT3 mutation (P=0.002) and NPM1 mutation (P༝0.001)were more likely to be seen in the high CD33 group. ③ The overall survival (OS) was worse in the high CD33 group (39.0 m vs. 16.7 m, x2 = 7.385, P = 0.007). Multivariate analysis showed that the high expression of CD33 was an unfavorable prognostic factor. ④ Of the 86 patients, CD33-high was closely related to the patients with normal karyotype (x2 = 4.891,P = 0.027), high white blood cell count (WBC, t = 2.804, P = 0.007), and a high ratio of primitive cells (t = 2.851, P = 0.005). Conclusions These findings provide a strong rationale for targeting CD33 in combination with chemotherapy, which can be considered a promising therapeutic strategy for AML.

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Predictors of Faster Decline of Residual Renal Function in Taiwanese Peritoneal Dialysis Patients

Peritoneal Dialysis International ◽

10.1177/089686080802803s35 ◽

2008 ◽

Vol 28 (3_suppl) ◽

pp. 191-195 ◽

Cited By ~ 3

Author(s):

Chia-Te Liao ◽

Chih-Chung Shiao ◽

Jenq-Wen Huang ◽

Kuan-Yu Hung ◽

Hsueh-Fang Chuang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Renal Function ◽

Peritoneal Dialysis ◽

Clinical Laboratory ◽

Statistical Significance ◽

Univariate Analysis ◽

Residual Renal Function ◽

Measure Data ◽

Chi Square ◽

Artery Disease

⋄ Objective Loss of residual renal function (RRF) in peritoneal dialysis (PD) patients is a powerful predictor of mortality. The present study was conducted to determine the predictors of faster decline of RRF in PD patients in Taiwan. ⋄ Methods The study enrolled 270 patients starting PD between January 1996 and December 2005 in a single hospital in Taiwan. We calculated RRF as the mean of the sum of 24-hour urea and creatinine clearance. The slope of the decline of residual glomerular filtration rate (GFR) was the main outcome measure. Data on demographic, clinical, laboratory, and treatment parameters; episodes of peritonitis; and hypotensive events were analyzed by Student t-test, Mann–Whitney U-test, and chi-square, as appropriate. All variables with statistical significance were included in a multivariate linear regression model to select the best predictors ( p < 0.05) for faster decline of residual GFR. ⋄ Results All patients commencing PD during the study period were followed for 39.4 ± 24.0 months (median: 35.5 months). The average annual rate of decline of residual GFR was 1.377 ± 1.47 mL/min/m2. On multivariate analysis, presence of diabetes mellitus ( p < 0.001), higher baseline residual GFR ( p < 0.001), hypotensive events ( p = 0.001), use of diuretics ( p = 0.002), and episodes of peritonitis ( p = 0.043) independently predicted faster decline of residual GFR. Male sex, old age, larger body mass index, and presence of coronary artery disease or congestive heart failure were also risk factors on univariate analysis. ⋄ Conclusions Our results suggested that diabetes mellitus, higher baseline residual GFR, hypotensive events, and use of diuretics are independently associated with faster decline of residual GFR in PD patients in Taiwan.

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Blood Oxygenation Level Dependent Magnetic Resonance Imaging (MRI), Dynamic Contrast Enhanced MRI and Diffusion Weighted MRI for Benign and Malignant Breast Cancer Discrimination: A Preliminary Experience

Cancers ◽

10.3390/cancers13102421 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2421

Author(s):

Roberta Fusco ◽

Vincenza Granata ◽

Mauro Mattace Raso ◽

Paolo Vallone ◽

Alessandro Pasquale De Rosa ◽

...

Keyword(s):

Standard Deviation ◽

Univariate Analysis ◽

Mean Value ◽

Blood Oxygenation ◽

Breast Lesions ◽

Dce Mri ◽

Malignant Lesions ◽

The Mean ◽

And Diffusion ◽

Skewness And Kurtosis

Purpose. To combine blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI), dynamic contrast enhanced MRI (DCE-MRI), and diffusion weighted MRI (DW-MRI) in differentiation of benign and malignant breast lesions. Methods. Thirty-seven breast lesions (11 benign and 21 malignant lesions) pathologically proven were included in this retrospective preliminary study. Pharmaco-kinetic parameters including Ktrans, kep, ve, and vp were extracted by DCE-MRI; BOLD parameters were estimated by basal signal S0 and the relaxation rate R2*; and diffusion and perfusion parameters were derived by DW-MRI (pseudo-diffusion coefficient (Dp), perfusion fraction (fp), and tissue diffusivity (Dt)). The correlation coefficient, Wilcoxon-Mann-Whitney U-test, and receiver operating characteristic (ROC) analysis were calculated and area under the ROC curve (AUC) was obtained. Moreover, pattern recognition approaches (linear discrimination analysis and decision tree) with balancing technique and leave one out cross validation approach were considered. Results. R2* and D had a significant negative correlation (−0.57). The mean value, standard deviation, Skewness and Kurtosis values of R2* did not show a statistical significance between benign and malignant lesions (p > 0.05) confirmed by the ‘poor’ diagnostic value of ROC analysis. For DW-MRI derived parameters, the univariate analysis, standard deviation of D, Skewness and Kurtosis values of D* had a significant result to discriminate benign and malignant lesions and the best result at the univariate analysis in the discrimination of benign and malignant lesions was obtained by the Skewness of D* with an AUC of 82.9% (p-value = 0.02). Significant results for the mean value of Ktrans, mean value, standard deviation value and Skewness of kep, mean value, Skewness and Kurtosis of ve were obtained and the best AUC among DCE-MRI extracted parameters was reached by the mean value of kep and was equal to 80.0%. The best diagnostic performance in the discrimination of benign and malignant lesions was obtained at the multivariate analysis considering the DCE-MRI parameters alone with an AUC = 0.91 when the balancing technique was considered. Conclusions. Our results suggest that the combined use of DCE-MRI, DW-MRI and/or BOLD-MRI does not provide a dramatic improvement compared to the use of DCE-MRI features alone, in the classification of breast lesions. However, an interesting result was the negative correlation between R2* and D.

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Colonoscopy does not induce small intestinal bacterial overgrowth

Journal of Digestive Endoscopy ◽

10.4103/0976-5042.202813 ◽

2017 ◽

Vol 08 (01) ◽

pp. 12-16

Author(s):

Ioana Gabriela Moraru ◽

Dan Lucian Dumitraşcu

Keyword(s):

Statistical Significance ◽

False Negative ◽

Bacterial Overgrowth ◽

Intestinal Bacteria ◽

Small Intestinal Bacterial Overgrowth ◽

Mean Value ◽

Intestinal Bacterial Overgrowth ◽

Gastrointestinal Pathology ◽

The Mean ◽

Small Intestinal

Abstract Background and Aim: Small intestinal bacterial overgrowth (SIBO) is associated with gastrointestinal pathology and colonoscopy. This endoscopic investigation could cause changes in gut flora including the occurrence of SIBO. We looked in this study for the effect of colonoscopy (preparation and intubation) on the occurrence of SIBO. Materials and Methods: Prospective study including thirty patients with irritable bowel syndrome (IBS) diagnosed according to Rome III criteria. Two groups were designed: Twenty IBS patients that performed colonoscopy (G1) and ten IBS patients (G2) not referred to colonoscopy. All patients have been tested for the presence of SIBO using glucose hydrogen breath tests (GHBT) at the beginning of the study, on day 1. G1 patients have also been tested before colonoscopy (day 2) and 1 week after (day 9). G2 patients performed GHBT on day 1 and on day 9. Results: The peak value of expired H2 was assessed, and the mean value was calculated. There were no significant statistical differences between the mean H2 values in the 2 groups of patients on day 1. The mean level of H2 significantly decreased after preparing for colonoscopy in G1 patients (P < 0.0001). There were no significant statistical differences between the mean levels of H2 on day 2 versus day 9 in G1 patients (P = 0.176). The mean level of H2 1 week after performing colonoscopy (7.65 ppm) is higher than that obtained after preparing for it (6.3 ppm), but no statistical significance. Patients from G2 showed no statistical differences between the mean levels of H2 on day 1 versus day 9 (P = 0.6132). Patients in G1 had a significantly lower mean H2 level versus G2 patients on day 9. Conclusions: Colonoscopy does not produce SIBO. Preparing for colonoscopy influences the level of expired H2, it reduces the number of intestinal bacteria, probably trough a mechanic effect or by inflating air during the procedure. Performing GHBT too soon after colonoscopy might result in false negative results of GHBT.

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Abstract 16884: Evaluating the Effectiveness of Atrial Fibrillation Ablation Guided by Spatiotemporal Electrogram Dispersion

Circulation ◽

10.1161/circ.142.suppl_3.16884 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Brian Liu ◽

Arismendy Nunez-Garcia ◽

Cao Tran ◽

Michael Wu

Keyword(s):

Atrial Fibrillation ◽

Atrial Tachycardia ◽

Statistical Significance ◽

Univariate Analysis ◽

External Validation ◽

Posterior Wall ◽

High Rate ◽

Single Center Experience ◽

The Mean

Introduction: Catheter ablation of atrial fibrillation (AF) guided by spatiotemporal dispersion (SD) of electrograms has been proposed as an ablation strategy to treat patients with persistent AF. However, external validation of this technique is lacking. Here we report a single center experience using ablation by SD. Hypothesis: Targeting regions with SD is associated with a high rate of termination and favorable freedom from AF among patients with persistent AF. Methods: Patients with persistent AF who underwent SD from November 2018 to January 2020 were included in this study. All patients underwent pulmonary vein isolation (PVI) in addition to targeting areas of SD. Lesions on areas of electrogram dispersion were anchored to the PVI or to mitral or posterior wall lines where appropriate. EKG, Holter, event monitors or device interrogations were obtained at 3 and 6 months to assess for arrhythmia recurrence. Results: 44 patients met the inclusion criteria and were included in the study. The patients had a mean age of 69±8 years and were 68 % male. The prevalence of comorbidities was as follows: hypertension (89%), diabetes (21%), OSA (37%) and CAD (26%). Average CHADSVASC score was 2.9±1.4, LVEF was 53±11% and left atrium (LA) diameter was 5.2±1 cm. The recurrence rate of AF at 6 months was 14% whereas the recurrence of atrial tachycardia was 20%. Acute AF termination was observed in 73% of the patients. Termination to sinus occurred in 38% of the patients and the remaining terminated to atrial tachycardia which was subsequently ablated to sinus. The mean procedure duration was 240±90 minutes. Univariate analysis showed recurrence was associated with LA diameter (r=.52; p<.001). No recurrences were observed among patients with a LA diameter < 5 cm. Termination rates were higher among patients with LA diameter < 5 cm when compared to LA diameter ≥ 5 cm. However, it did not reach statistical significance (80% vs. 60%; p=.21). Conclusions: The target of electrograms with SD during AF ablation added to PVI was associated with a high termination rate and a good freedom from AF recurrence at 6 months. The ideal candidate for this procedure may be those with LA diameter < 5 cm among persistent AF. The long-term efficacy of this technique merits further studies in larger populations.

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The significance of blood cell biomarkers in the prognosis of gastric cancer

10.21203/rs.3.rs-33702/v1 ◽

2020 ◽

Author(s):

Pu Huang ◽

Yiran Zhang ◽

Anqiang Wang ◽

Zhao-de Bu

Keyword(s):

Gastric Cancer ◽

Prognostic Factors ◽

Blood Cell ◽

Cox Regression ◽

Univariate Analysis ◽

Prognostic Significance ◽

Vascular Tumor ◽

Tumor Differentiation ◽

Chi Square ◽

Preoperative Serum

Abstract Background Studies have shown that inflammation-associated blood cell markers are associated with prognoses in a variety of tumors. However, the prognostic significance of these markers for gastric cancer (GC) is still not very clear. This article aims to explore its value of GC prognostic assessment.Methods From July 2011 to July 2016, 353 GC patients with surgical treatment were enrolled in this retrospective study. Patients’ demographics were analyzed along with clinical and pathologic data. The chi-square test was used to evaluate relationships between the markers and other clinicopathological variables; The Kaplan–Meier method and Cox regression proportional hazard model were performed to evaluate prognostic factors.Results Univariate analysis indicated T stage, N stage, vascular tumor thrombus, tumor long diameter, Bormann Classification, preoperative MWR (monocyte/leukocyte ratio), preoperative serum CEA levels are prognostic factors for GC. Multivariate analysis showed that preoperative MWR, tumor differentiation, and tumor length were independent prognostic factors in patients with GC. The boundary value of MWR is 0.8.Conclusion Preoperative MWR was convenient, simple marker of gastric cancer, might be useful for the evaluation of prognosis of patients with GC. Comparing with TNM stage, tumor differentiation was a more reliable pathological factor evaluating recurrence.

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Arthroscopic Bristow: 12-Year Experience, Assessments of Safety and Effectiveness

Revista Brasileira de Ortopedia ◽

10.1055/s-0039-1697972 ◽

2019 ◽

Author(s):

Jose Carlos Garcia

Keyword(s):

Los Angeles ◽

Shoulder Instability ◽

De Novo ◽

Mean Value ◽

Anterior Shoulder Instability ◽

Simple Shoulder Test ◽

The Mean ◽

Lateral Rotation ◽

Clinically Significant

Abstract Objective The open Bristow procedure is a long established and effective method for treating anterior shoulder instability. Following the trends of minimally-invasive surgeries, these procedures were performed arthroscopically, and their outcomes were evaluated. Methods A total of 43 shoulders of patients submitted to Bristow procedures by arthroscopy, using a graft positioned horizontally and a screw, with at least two years of postoperative follow-up, were evaluated regarding quality of life, de novo dislocation index, and loss of lateral rotation. Results The mean follow-up time was of 76 months (range: 129 to 24 months). The University of California at Los Angeles (UCLA) score varied from 25.56 ± 0.50 (standard deviation [SD] = 3.25) to 33.23 ± 0.44 (SD = 2.91) (p < 0.0001). Two or more years after surgery, the mean Rowe score was of 94.25 ± 1.52 (SD = 1.34), whereas the good results standard is 75 (p < 0.0001). The mean value for the simple shoulder test was of 11.35 ± 0.21 (SD = 1.34), while the mean value of the lateral rotation loss was of 10.37° ± 1.36° (SD = 8.58°). There were no de novo dislocations.In total, there were 12 complications, 8 of which had no clinical repercussions. The clinically-significant complications included an infection six months after surgery with a potential hematogenous origin, a coracoid fracture that required an intraoperatively procedure change, and two patients with previous impingement who required synthesis material removal more than six months after surgery. Conclusion Although the arthroscopic Bristow procedure was effective in treating anterior shoulder instability, it is not a complication-free surgery.

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Two-Year Outcomes of Orbital Atherectomy Combined With Drug-Coated Balloon Angioplasty for Treatment of Heavily Calcified Femoropopliteal Lesions

Journal of Endovascular Therapy ◽

10.1177/1526602820915244 ◽

2020 ◽

Vol 27 (3) ◽

pp. 492-501 ◽

Cited By ~ 2

Author(s):

Damianos G. Kokkinidis ◽

Omar Jawaid ◽

David Cantu ◽

Brad J. Martinsen ◽

Zsuzsanna Igyarto ◽

...

Keyword(s):

Cox Regression ◽

De Novo ◽

Combined Therapy ◽

Statistical Significance ◽

Retrospective Chart Review ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Effective Combination ◽

Orbital Atherectomy ◽

Procedural Complications

Purpose: To examine whether the combination of orbital atherectomy (OA) and drug-coated balloons (DCB) can lead to superior procedural and 2-year outcomes compared with DCB only in heavily calcified femoropopliteal (FP) lesions. Materials and Methods: A retrospective chart review was conducted to identify patients treated with DCB only or OA+DCB for de novo FP lesions at a single center over a 4-year period (2014–2017). In the observation period, 113 patients met the inclusion criteria: 63 treated with DCB only (mean age 69.0±8.6 years; 62 men) vs 50 treated with OA+DCB (mean age 70.3±7.1 years; 48 men). The OA+DCB group had higher calcification rates (78% with severe calcification vs 37% in the DCB only group). Propensity score matching (PSM) was used to adjust for baseline differences between the 2 groups. Cox regression analysis was used to compare the follow-up outcomes between lesions treated with OA+DCB vs DCB only. Results: No difference in procedural complications or success was found. After PSM adjustment, the OA+DCB group was associated with lower bailout stenting rates (39.4% vs 66.7% in the DCB only group; p=0.026). The 2 groups had similar long-term outcomes, although the OA+DCB arm had a trend toward reduced TLR rates that did not reach statistical significance. The Kaplan-Meier estimates for 2-year freedom from TLR were 76.1% for the OA+DCB group vs 55.5% for the DCB only group (p=0.109). Conclusion: OA+DCB is a safe and effective combination for the treatment of calcified FP lesions. The combined therapy decreased the bailout stenting rates in the adjusted analysis. Larger cohorts and randomized trials are needed to examine OA efficacy in FP lesions.

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Pie Crust Technique of the Deep Medial Collateral Ligament in Knee Arthroscopy: Ultrasound and Anatomic Study

The Journal of Knee Surgery ◽

10.1055/s-0038-1668125 ◽

2018 ◽

Vol 32 (08) ◽

pp. 764-769

Author(s):

Guillem Claret-Garcia ◽

Jordi Montañana-Burillo ◽

Eduard Tornero-Dacasa ◽

Manel Llusá-Pérez ◽

Dragos Popescu ◽

...

Keyword(s):

Medial Collateral Ligament ◽

Statistical Significance ◽

Mean Value ◽

Saphenous Nerve ◽

Medial Compartment ◽

P Value ◽

Collateral Ligament ◽

Anatomical Dissection ◽

Ultrasound Measurements ◽

The Mean

AbstractThis article determines compartment opening of the medial articular space of the knee after pie crust (PC) technique of the medial collateral ligament (MCL) by ultrasound measurements and anatomic dissection. This is a cadaveric study of 12 specimens. Four anatomic references were marked on the skin. Distances between the femur and tibia in the internal compartment at 30 degrees of flexion were obtained with ultrasound measurements in four situations: with and without applying valgus force both prior and after the PC technique. Ultrasound measurements of the medial articular compartment were made twice and mean value was calculated. An anatomical dissection was performed and distances between the puncture marks and the infrapatellar branch of the saphenous nerve was measured. Lilliefors test of normality was applied and variables were expressed as mean and standard deviation (SD). Qualitative variables were expressed by absolute frequencies and percentages. Statistical significance was a two-tailed p-value of < 0.05. Prior to the PC technique, mean (SD) distance between the femur and tibia in the medial compartment were 14.2 (4.0) mm in basal conditions and 17.1 (3.7) mm when applying valgus force (p = 0.003). PC technique increased the mean (SD) distance by 1.9 (1.9) mm under basal conditions (p < 0.01) and 2.9 (1.6) mm when applying valgus force (p < 0.01). The infrapatellar branches of the saphenous nerve were not damaged and the mean (SD) distance between the punctures and the nerve was 9.0 (3.3) mm. The PC is a reproducible, safe, and measurable surgical technique that opens controllably the medial compartment. PC as described avoided damage to the nerve branches.

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Impact of age and gender in patients with thin melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.8056 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 8056-8056 ◽

Cited By ~ 1

Author(s):

C. K. Chang ◽

S. K. Liu ◽

J. S. Choi ◽

R. C. Liu ◽

P. F. Fuchshuber

Keyword(s):

Cox Regression ◽

Univariate Analysis ◽

Age Groups ◽

Rank Test ◽

Superficial Spreading ◽

Chi Square ◽

Age And Gender ◽

Thin Melanoma ◽

Male Ratio ◽

And Gender

8056 Background: The incidence of thin melanoma (≤ 1mm) continues to increase. The purpose of this study was to characterize the incidence and prognosis of thin melanoma among the various age groups. We analyzed the records of 15,267 patients diagnosed with melanoma of these we were able to identify 5573 patients with thin melanoma (≤ 1mm). Methods: A retrospective review was undertaken to identify patients with thin melanoma (<1mm) treated at all the Northern California Kaiser Permanente facilities. All patients received their treatment between January 1998 and December 2004. Univariate and multivariate analyses of predictive factors were evaluated with the log-rank test and Cox regression. In addition chi-square test of relevant clinicopathologic factors determined which factors were predictive of overall survival (OS). Results: Mean age was 55 years (range 8–101). Mean follow-up was 74 months (range 3–209) and 54% were male. Primaries were on the trunk (34%), lower extremities (19%), upper extremities (26%), or head/neck (20%). Mean thickness was 0.4 ± 0.25 mm. The most common histology was superficial spreading (88%). The overall 5 and 10 year survival were 89 and 79, respectively. By univariate analysis age, sex, location and histology were predictive of OS however by multivariate analysis only age and sex were predictive of OS. The female/male ratio was 2 in patients diagnosed before the 3rd decade, and this ratio approached 1 in the mid-5th decade. However, the female/male ratio was 0.5 among patients diagnosed with melanoma in their 8th decade. Conclusions: Females are more susceptible than men to the risk of melanoma at a younger age however this susceptibility changes with increasing age. Our results demonstrate that the incidence of melanoma may be influenced by age and gender. No significant financial relationships to disclose.

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