Citations

Abstract Daratumumab in combination with lenalidomide‐dexamethasone (D‐Rd) recently received FDA approval for the treatment of transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression‐free survival (PFS) in patients treated with D‐Rd in the MAIA trial and patients treated with common standard‐of‐care regimens from the Flatiron Health electronic health record‐derived deidentified database, which has data from patients treated primarily at community‐based oncology practices in the United States. Individual‐level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D‐Rd to bortezomib‐lenalidomide‐dexamethasone (VRd) and bortezomib‐dexamethasone (Vd); lenalidomide‐dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D‐Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D‐Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity‐score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D‐Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D‐Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head‐to‐head trials comparing D‐Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant‐ineligible patients with NDMM.

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

Abstract Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. The aim of this study is to determine the association of IL-17A -197G/A polymorphism with RA in Sudanese Patients. A descriptive cross-sectional study was conducted between March and December, 2018. Clinical and demographic data of the study participants were collected and analysed. All statistical tests were considered as statistically significant when p < 0.05.Results: The study population included 266 participants, 166 (63.1%) were females [mean age 41.4 ± 15.5 years] and 97 (36.9%) were males [mean age 36.2 ± 16.0 years]. Of the 266 participants, 31% (85/266) were RA cases and 69% (181/266) were healthy controls. Prevalence of IL-17A genotypes among the study population was 52.6% (140/266) were AG heterozygote genotype, 38.4% (102/266) were AA homozygote genotype, and 9.0% (24/266) were GG homozygote genotype. Correlation of IL-17A genotypes was negatively statistically significant based on participants clinical status, and family history of RA, Pearson’s correlation [r = -0.392, P value 0.001] and [r = -0.226, P value 0.001], respectively, while positively statistically significant with gender, Pearson’s correlation [r = 0.140, P value 0.023]. Based on the duration of RA, no statistically significant correlation was observed, Pearson’s correlation [ r = -0.138, P value 0.207].

Abstract Purpose: TNF-related apoptosis inducing ligand (TRAIL) expression by immune cells contributes to antitumor immunity. A naturally occurring splice variant of TRAIL, called TRAILshort, antagonizes TRAIL-dependent cell killing. It is unknown whether tumor cells express TRAILshort and if it impacts antitumor immunity. Experimental Design: We used an unbiased informatics approach to identify TRAILshort expression in primary human cancers, and validated those results with IHC and ISH. TRAILshort-specific mAbs were used to determine the effect of TRAILshort on tumor cell sensitivity to TRAIL, and to immune effector cell dependent killing of autologous primary tumors. Results: As many as 40% of primary human tumors express TRAILshort by both RNA sequencing and IHC analysis. By ISH, TRAILshort expression is present in tumor cells and not bystander cells. TRAILshort inhibition enhances cancer cell lines sensitivity to TRAIL-dependent killing both in vitro and in immunodeficient xenograft mouse models. Immune effector cells isolated from patients with B-cell malignancies killed more autologous tumor cells in the presence compared with the absence of TRAILshort antibody (P &lt; 0.05). Conclusions: These results identify TRAILshort in primary human malignancies, and suggest that TRAILshort blockade can augment the effector function of autologous immune effector cells. See related commentary by de Miguel and Pardo, p. 5546

Abstract Objectives The persistence of high-risk Human Papilloma virus-16 (HPV-16) is considered as a predisposing factor for the development of the cervical carcinoma and the prognosis of the disease. However, other multifactorial risk factors including cell proliferation and apoptosis markers were also studied and linked to the development and progression of cervical carcinoma. This study is aiming at investigating the association between the presence of HPV-16 and the expression of p53 and Bcl-2 in benign and malignant cervical lesions using immunohistochemical staining methods. Results A total of 150 cases with different cervical lesions were studied, their age ranges from 34 to 67 years (mean 49.5 ± 6.9). Out of the 150 cases; 97 (64.7%) were malignant, 37 (24.7%) were pre-cancerous and 16 (10.7%) were benign lesions. The association between the expression of Bcl-2 and p53, the different histopathological diagnosis, and the type of lesion was statistically significant (p value < 0.0001) Furthermore the statistical analysis of Bcl-2 expression revealed a significant correlation with the cancer grade (p value = 0.018). Nevertheless, p53 expression showed no association with the cancer grade. Regarding the correlation between the presence of HPV-16 and the markers the results were found to be statistically significant.

AbstractTransplant‐associated thrombotic microangiopathy (TA‐TMA) has a wide range of presentations after hematopoietic stem‐cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA‐TMA. Among the 1451 HSCT recipients, early TA‐TMA occurred in 45 (3.1%) patients at a median of 27 (3‐91) days, and late TA‐TMA in 39 (2.7%) patients at a median of 303 (122‐2595) days. Patients with early TA‐TMA were more likely to have high blood calcineurin‐inhibitor levels (P < .001) and acute graph‐vs‐host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00‐1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98‐6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16‐0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03‐0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02‐0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.

Abstract Objectives: Infection with the bacteria Helicobacter pylori has been classified as class one carcinogen associated with increasing susceptibility of gastritis and gastric carcinoma. This study is aiming at investigating the prevalence of H. pylori among colon polyps and colon cancer patients. A descriptive cross-sectional hospital-based study was conducted between February and June 2017. Sixty-nine formalin-fixed paraffin blocks collected from colon polyps and colon cancer patients to detect H. pylori using immunohistochemistry technique. Results: Of the Sixty-nine patients included in the study, 39 (56.5%) males and 30 (43.5%) were females, their age ranged from 21 to 80 years with a mean age of 47.1±19.7. Of the 69 colon polyps and colon cancer patients, 44 (63.8%) were diagnosed as adenocarcinoma, 10 (14.5%) colitis, 15 (21.7%) juvenile polyposis syndrome. The results of immunohistochemistry technique showed the presence of 16 (23.2%) positive patients for H. pylori infection. Of these 16, 13 (81.3%) patients were diagnosed with adenocarcinoma and 3 (18.7%) patients were diagnosed with juvenile polyps. The results of H. pylori detection among the different colon polyps and colon cancer patients were showing a statistically significant association for H. pylori infection and adenocarcinoma, P value 0.028.

Objective: To compare the clinical outcomes of static versus dynamic external fixation for elbow fracture-dislocations with persistent instability after surgical management. Design: Comparative, retrospective review. Setting: Two tertiary referral upper-extremity centers. Patients: Twenty-four elbows requiring external fixation for persistent elbow instability within 90 days of surgical management of an elbow fracture-dislocation. Intervention: Static and dynamic external fixation was used in 16 and 8 patients, respectively, for a median of 39 days (interquartile range, 33–48 days). Main Outcome Measurements: Elbow range of motion, complications, and revision surgeries. Results: Immediately after static and dynamic external fixation removal, there was no difference in elbow extension [33 degrees ± 16 degrees vs. 41 degrees ± 13 degrees, mean difference (MD) 7 degrees, 95% confidence interval (CI) −6 degrees–22 degrees] or flexion (114 degrees ± 35 degrees vs. 118 degrees ± 11 degrees, MD 4 degrees, 95% CI -23 degrees–132 degrees), respectively. At last follow-up, static and dynamic external fixation groups had no difference in elbow extension (27 degrees ± 13 degrees vs. 24 degrees ± 10 degrees, MD -3 degrees, 95% CI –15 degrees–7 degrees) or flexion (129 degrees ± 12 degrees vs. 128 degrees ± 14 degrees, MD -1 degree, 95% CI -13 degrees–10 degrees), respectively. Static and dynamic external fixation groups had no difference in complications [7 (44%) vs. 5 (63%), difference 19%, 95% CI -23%–54%] or revision surgeries [6 (38%) vs. 4 (50%), difference 13%, 95% CI -27%–49%]. Conclusions: No difference in range of motion, complications, and revision surgeries was detected after static versus dynamic external fixation of persistently unstable elbow fracture-dislocations. Due to ease of application, static external fixation is our preferred treatment for these injuries. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.