Pre-exposure vaccination in the high-risk population is crucial in controlling mpox resurgence in Canada.

PURPOSE: Although the Bacille Calmette-Guerin (BCG) vaccine is widely used in many developing countries, it has limited efficacy in preventing tuberculosis (TB). Of the newer TB vaccines which are currently being developed, some are intended to prevent disease in uninfected persons (pre-exposure vaccines) and others are intended to prevent the development of disease in latently infected persons (post-exposure vaccines.) We predict the impact that mass vaccination campaigns with moderate to high efficacy pre-exposure and post-exposure vaccines would have on the TB epidemic in India. We calculate the effect that these vaccines would have on the the incidence of active TB and the death rate from TB in India over twenty years. METHODS: We use mathematical models to make our predictions. Two models of TB epidemics are developed to represent the population effects of pre-exposure and post-exposure vaccines. Each model includes the various ways in which a vaccine may be fail: immunity may be conferred to only some of those vaccinated; immunity may only be partially protective to those who acquire it; immunity may wane over time. Time-dependent uncertainty and sensitivity analysis is performed using latin hypercube sampling, a stratified form of Monte Carlo sampling. This analysis enables us to include uncertainty in multiple parameters and transform this into prediction uncertainty. The sensitivity analysis is carried out over time to determine the vaccine characteristics and population parameters most important in determining the vaccines'impact at different time intervals. RESULTS: The model reveals that in general a post-exposure vaccine will have greater impact than a pre-exposure vaccine on the incidence of active TB and death from TB. For example, if the initial annual incidence of active TB is 187 cases per 100,000 persons then a post-exposure vaccine which is applied to 60-90% of the population and which has 50–80% efficacy and an average waning time of 10–30 years will reduce the annual incidence by a median of 33.6% (2.5th percentile 18.3% - 97.5th 62.8%) over 20 years. In contrast a pre-exposure vaccine applied to a population with the same initial incidence and the same efficacy, coverage rate, and waning rate will reduce the incidence by a median of 16.5% (2.5th percentile 11.6% - 97.5th 24.3%) over 20 years. A post-exposure vaccine will also be more effective in reducing the death rate from TB over 20 years. CONCLUSION: A post-exposure vaccine is likely to make the greatest impact on reducing the rate of active TB and death from TB in India.

Racial Comparisons of Prostate Cancer Outcomes in a Unique Military Patient Population Post-Definitive External Beam Radiation Therapy

Development of a Combined Risk Assessment Model for Venous Thromboembolism and Bleeding in Hematopoietic Stem Cell Transplantation Patients

e18581 Background: While most patients (pts) with HR+, HER2- early breast cancer (EBC) do not experience disease recurrence, those with high risk clinicopathologic features may have recurrence within the first few years on adjuvant endocrine therapy (AET). This study estimates risk of recurrence in pts with EBC based on clinicopathologic features and evaluates the medical need for more efficacious treatments using US oncology practice data. Methods: This retrospective study used the nationwide Flatiron Health electronic health record derived deidentified database. The cohort included pts with HR+, HER2- stage I-III breast cancer, diagnosed Jan 2011-Mar 2020, who received surgery and AET. Clinicopathologic features were used to identify a ‘high risk (HiR) group’ (≥ 4 positive axillary lymph nodes (LN), or 1-3 positive axillary LN and ≥ 1 of the following: Grade 3, tumor size ≥ 5 cm, or Ki-67 ≥ 20%) and ‘low risk (LoR) group’ (pts who do not meet above criteria, including a subset with node negative (N0) disease). Cox proportional hazards regression models compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from AET initiation between groups according to a sequential gatekeeping strategy and stepwise analysis: first compare HiR group to N0 pts; if significant then compare HiR to LoR group. Results: 557 (13.8%) pts were in the HiR group and 3,471 (86.2%) in the LoR group (including 2,867 N0 pts). The study population (median age 64 yrs) was predominantly female (99.2%), white (69.4%) and postmenopausal (75.6%) with median follow-up of 39.6 months. Pts in the HiR group were younger and more likely premenopausal, have a BRCA mutation, invasive lobular carcinoma and less likely to have received an Oncotype DX test compared to LoR pts. Of the 557 HiR pts, 231 (41.5%) had ≥ 4 positive LN and 326 (58.5%) had 1-3 positive axillary LN with additional risk factor(s): tumor size ≥ 5 cm (11.7%), histologic grade 3 (32.0%), and/or Ki-67 ≥ 20% (31.6%). Most HiR pts received radiotherapy (82.4%) and chemotherapy (68.1%). Significant differences in IDFS and DRFS were observed between HiR group and N0 and LoR groups (logrank test p < .0001 for all). The 2-year IDFS rate was 88.1% in the HiR group, compared to 97.4% in N0 pts and 97.1% in the LoR group; 2-year DRFS rates were 89.0% compared to 97.9% and 97.7%, respectively. Pts in the HiR group had significantly higher hazard of invasive disease recurrence or death compared to N0 (HR = 3.42, 95% CI: 2.69-4.34, p < .0001) and LoR group (HR = 3.07, 95% CI: 2.46-3.84, p < .0001). Similar results observed for DRFS (HiR vs N0: HR = 3.46, 95% CI: 2.70-4.44, p < .0001; HiR vs LoR HR = 3.16, 95% CI: 2.50-3.98, p < .0001). Conclusions: Approximately 12% of pts with EBC and high risk clinicopathologic features experienced invasive disease recurrence or death within 2 years of initiating AET. Optimal use of standard therapies and novel treatment options are needed to prevent early recurrence and metastases in these pts.

APPLICATION of EUTOS SCORE IN CHRONIC Myeloid LEUKEMIA AFFECTING VERY Elderly (>75 years) PATIENTS

Background: Bronchial asthma is characterized by lower respiratory tract inflammation associated with bronchial hyper responsiveness with variable and reversible airflow obstruction. The majority of asthmatics are sensitized to at least one common allergen. Aim of the study: The aim of this study is to determine the association of high-risk asthma with allergy-related parameters (total serum IgE levels, serum levels of allergen- specific IgE, eosinophil count, eosinophil percentage ) and pulmonary functions in children. Subjects and methods: 50 Children aged 8-15 years diagnosed with atopic asthma were enrolled in the study. Pulmonary function tests, total leukocyte count (TLC), eosinophil count, and eosinophil percentage were estimated. Total serum immunoglobulin E (IgE) levels and serum IgE levels specific to antigens from 1 to 9 allergens with class 1 or higher, namely, Dermatophagoides pteronyssinus (D. pteronyssinus) , Dermatophagoides farina (D. farina ), cat dander , dog dander, cockroach, egg white, milk, Aspergillus fumigatus, and fish, were measured using UniCAP fluoroenzyme immunoassay (FEIA). Results: This study includes 50 participants, 20 (40%) belonged to the high-risk and 30 (60%) to the low-risk groups. This study revealed no significant association in peak expiratory flow rate (PEFR, ％) values between high-risk and low-risk asthma groups (p ˃ 0.05). There was no significant association in forced expiratory volume in first second [ FEV1 (L)] values between high-risk and low-risk asthma groups ( p ˃ 0.05), whereas there was significant association in FEF 25-75% (forced expiratory flow 25-75%) values between high-risk and low-risk asthma groups ( p ˂ 0.05). There was a significant association between total serum IgE level and high-risk asthma, but TLC, eosinophil count, and eosinophil percentage showed non significant association with high-risk asthma. Serum levels of IgE specific to D. pteronyssinus, D. farina, cat dander, and dog dander were significantly associated with high-risk asthma. The high-risk group had higher serum levels of IgE specific to D. pteronyssinus ( p < 0.0001), D. farina ( p < 0.0001), cat dander ( p < 0.0001), and dog dander antigens ( p < 0.0001) compared with those in the low-risk group. There was no significant association between high-risk asthma and the serum levels of IgE specific to antigens from other allergens (including cockroach, egg white, and milk). Serum levels of IgE specific to Aspergillus fumigatus and fish were both negative (class level < 1) in both the high-risk group and the low-risk group. Conclusion Children with higher serum levels of IgE specific to D.pteronyssinus, D. farina, cat dander and dog dander antigens, and total serum IgE levels, and lower FEF25-75% values belong to the high-risk asthma group. The characterization of risk factors has enabled us to identify high-risk asthma in children , leading to better treatment options.

Prognostic role of FDG-PET in outcomes of relapsed/refractory large B-cell lymphoma treated with CD3-CD20 directed bispecific antibodies

This systematic review and meta-analysis study was conducted to estimate the pooled prevalence of CD in low and high risk groups in this region. Following keywords were searched in the Medline, PubMed, Scopus, Web of Science and Cochrane database according to the MeSH terms; celiac disease, prevalence, high risk population and Asian-Pacific region. Prevalence studies published from January 1991 to March 2018 were selected. Prevalence of CD with 95% confidence interval (CI) was calculated using STATA software, version 14. The pooled sero-prevalence of CD among low risk group in Asia–Pacific region was 1.2% (95% CI 0.8–1.7%) in 96,099 individuals based on positive anti-tissue transglutaminase (anti-t-TG Ab) and/or anti-endomysial antibodies (EMA). The pooled prevalence of biopsy proven CD in Asia–Pacific among high and low risk groups was 4.3% (95% CI 3.3–5.5%) and 0.61% (95% CI 0.4–0.8%) in 10,719 and 70,344 subjects, respectively. In addition, the pooled sero-prevalence and prevalence of CD in general population was significantly higher in children compared with adults and it was significantly greater in female vs. male (P < 0.05). Our results suggest high risk individuals of CD are key group that should be specifically targeted for prevention and control measures, and screening may prove to have an optimal cost–benefit ratio.

To investigate the relationship between the type of FⅧgene mutation and the development of FⅧ inhibitors in patients with severe haemophilia A (HA). The medical records of 172 patients with severe hemophilia A from January 2009 to September 2020 were reviewed. The types of FⅧgene mutations and the production of factor Ⅷ inhibitors were collected and divided into high-risk mutation group ( intron 1 inversions, large deletions, nonsense mutations), low-risk mutation group (missense mutations, small deletions and insertions, splice site mutations) and intron 22 inversions group. The correlation of FⅧgenotype and the production of FⅧ inhibitors in patients with HA were analyzed. Among 172 patients with severe HA, 21 cases(12.21%) developed FⅧ inhibitors. The cumulative incidence of FⅧ inhibitor development was 32%(10/31) in high risk group (75% patients with large deletions, 43% patients with intron 1 inversions, 20% patients with nonsense mutations) and 5%(2/43) in low risk group(6% patients with missense mutations, 5% patients with small deletions or insertions and 0% patient with a splice site mutation) and 9%(9/98) in intron 22 inversions group. Compared with the risk of FⅧ inhibitor development in intron 22 inversions group, the risk of FⅧ inhibitor development in high risk group was higher (OR＝4.7, 95% CI： 1.7-13.0), the risk of FⅧ inhibitor development in low risk group was equal (OR＝0.5, 95% CI： 0.1-2.3). Compared with the risk of inhibitor development in low risk group, the risk of FⅧ inhibitor development in high risk group was higher (OR＝9.8, 95% CI： 2.0-48.7). Gene mutations of patients with severe HA in high-risk group which include intron 1 inversions, large deletions, nonsense mutations are a risk factor for FⅧ inhibitor production.

BackgroundLocal and generalized bone loss in patients with rheumatoid arthritis (RA) is a manifestation of disease progression or a negative consequence. Various endogenous and exogenous factors have an effect on...

Mantle Cell Lymphoma International Prognostic Score Is Valid and Confirmed in Unselected Cohort of Patients Treated in Rituximab Era

Objective: To investigate the prognostic value of SYNTAX score on 1 year outcome in coronary heart disease patients underwent percutaneous coronary intervention(PCI). Methods: The present study (PANDA Ⅲ trial) was a perspective, multi-center, randomized controlled trial. Between December 2013 and August 2014, 2 348 patients who underwent PCI from 46 centers were enrolled. SYNTAX score was calculated from all patients. Patients were divided into 3 groups based on SYNTAX score: lower risk group (SYNTAX score≤22, 1 777 patients), intermediate risk group (SYNTAX score 23-32, 412 patients), and higher risk group (SYNTAX score≥33, 159 patients). The patients were followed up after the procedure for one year.Primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction,and ischemia driven target lesion revascularization. Secondary endpoints included stent thrombosis and major adverse cardiac events were defined as a composite of all-cause death, myocardial infarction and any revascularization. Results: (1) A total of 1 766 (99.2%), 411 (99.8%),and 159 (100%) patients in the lower risk group, intermediate risk and higher risk group completed the 1 year follow up. (2) Incidence of TLF were 5.6%(99/1 763) in lower risk group, 8.8%(36/411) in intermediate risk group,and 8.8%(14/159) in higher risk group(P=0.03). The incidence of target vessel myocardial infarction in lower risk group was 3.9%(68/1 763), 6.6%(27/411) in intermediate risk group,and 7.5% (12/159) in higher risk group(P=0.01).Prevalence of cardiac death and ischemia driven target lesion revascularization was similar among the 3 groups(P>0.05).(3) The probable stent thrombosis events rate was 0.1% (1/1 763), 0.7% (3/411), and 0.6% (1/159) in the lower, intermediate,and higher risk groups respectively (P=0.02). The incidence of major adverse cardiac events was 8.1% (142/1 763) in lower-risk group, 11.7% (48/411) in intermediate risk group, and 14.5% (23/159) in higher risk group (P<0.01). The incidence of all-cause death was 1.7%(30/1 763) in lower-risk group, 1.7%(7/411) in intermediate risk group, and 6.3%(10/159)in higher risk group (P<0.01). The incidence of myocardial infarction was 4.2% (74/1 763) in lower-risk group, 6.6% (27/411) in intermediate risk group, and 8.2% (13/159) in higher risk group(P=0.02).Incidence of any revascularization was similar among groups(P=0.59). (4) The multivariable Cox analysis showed that age (HR=1.04, 95%CI 1.02-1.06, P<0.01), total implanted stent length (HR=1.01, 95%CI 1.00-1.02, P=0.03), and baseline SYNTAX score (HR=1.02, 95%CI 1.02-1.04, P=0.02) were independent risk factors of TLF after PCI in this patient cohort. Conclusion: The SYNTAX score is a valuable tool for predicting prognosis on 1 year in coronary heart disease patients underwent PCI. Trial Registration www.clinicaltrials.gov, NCT02017275.

High ABCD2-score after transient ischemic attack is associated with a two-fold higher stroke-rate during long-term follow-up

To Bleed or Not to Bleed. A Prediction Based on Individual Gene Profiling Combined With Dose–Volume Histogram Shapes in Prostate Cancer Patients Undergoing Three-Dimensional Conformal Radiation Therapy

To assess and compare the performance of acute physiology and chronic health evaluation II/IV (APACHEII/IV) prognostic models in elderly patients with sepsis. A totally of 82 elderly patients with sepsis were retrospectively assessed in geriatric intensive care unit of General Hospital of Guangzhou Military Command between July 2011 and December 2011. APACHEII/IV scores were recorded within 24 hours after admission. The prognosis accuracy of both scores was assessed by area under the receiver operating characteristic curve (AUC). Based on the best cutoff value corresponding with the highest accuracy, patients were divided into the low and high risk of hospital mortality group. The predictive power of APACHEII/IV in total population and subgroups was compared. Patients with severe sepsis constituted 57.3% (47/82) of all patients with sepsis, and hospital mortality was 61.0% (50/82). APACHEII/IV scores of the patients were 17.5±6.3 and 55.8±22.3, and mortality rate was 22.5% (18.4/82) and 17.9% (14.6/82) respectively, with significant differences compared with actual mortality (both P<0.01). Both APACHEII/IV scores showed underestimation of hospital mortality in total population [standardized mortality ratio (SMR) with APACHEII=2.71, 95% confidence interval (95%CI) 1.92-3.48 and SMR with APACHEIV=3.33, 95%CI 2.79-4.37]. APACHEII (AUC 0.664±0.066), and APACHEIV presented poor estimation(AUC 0.716±0.056). There was no difference in accuracy in prognosticating hospital death prognosis between the two APACHE models (Z=0.991, P=0.322). Cutoff values of APACHEII/IV were >11 and >59. According to the value, patients were divided into the low and high risk hospital mortality group. There was no significant difference between actual mortality and prognostic mortality in APACHEII low risk group [0-11, 20.0% (3/15) vs. 1.6% (0.2/15), Z=-1.023, P=0.306]. The actual mortality in high risk group with APACHEII (>11) was significantly higher than prognostic mortality [70.1% (47/67) vs. 27.2% (18.2/67), t=6.989, P=0.000]. In the high risk group, APACHEII underestimated mortality (SMR=2.58, 95%CI 2.22-3.51). The actual mortality of the low (0-59) and high (>59) risk group of APACHEIV were higher than prognostic mortality [lower risk group: 44.0% (22/50) vs. 7.5% (3.8/50), Z=-2.235, P=0.025; higher risk group: 87.5% (28/32) vs. 34.1% (10.9/32), Z=-4.712, P=0.000]. Two groups of patients with APACHEIV score, the mortality was underestimated (low risk group: SMR=5.90, 95%CI 5.19-7.07; high risk group: SMR=2.56, 95%CI 2.07-3.24). Mortality rate of the low risk group with APACHEIV score was prone to be underestimated. The accuracy of APACHEII/IV are not ideal in foretelling mortality rate. Hospital mortality was underestimated with APACHEII in high risk patients, and it was underestimated with APACHEIV both in low and high risk patients, and it is even more prone to be underestimated in low risk group of APACHEIV. More accurate prognostic modality is in need in elderly patients with sepsis.