Cytomegalovirus (CMV) disease is a major cause of infectious complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although patients undergoing allo-HSCT receive prophylactic and preemptive treatment for CMV, a subset of patients experience clinically significant CMV disease. This study investigated the risk factors for progression from CMV viremia to CMV disease during or after preemptive therapy in patients undergoing allo-HSCT. Between January 2006 and August 2010, 43 patients received preemptive therapy for CMV viremia after allo-HSCT. These patients experienced 74 episodes of CMV viremia. Nine of the patients (21%) and 12 of the episodes (16%) progressed to CMV disease. Univariate analysis identified several risk factors for progression to CMV disease, including high initial viral load (P = .020), leukopenia (P = .012), and neutropenia (P = .033) at the time of detection of CMV viremia. On multivariate analysis, leukopenia remained an independent predictor (hazard ratio, 4.347; P = .045). The rate of failure to clear CMV viremia after 1 cycle of preemptive therapy was higher in the leukopenia group than in the non-leukopenia group (60.0% versus 16.9%; P = .002). This indicates that leukopenia initially documented with CMV viremia is related to lower viral response to preemptive therapy and is a notable risk factor for progression from CMV viremia to CMV disease.
Although several human clinical trials using various bone marrow-derived cell types for cirrhotic or decompensated patients have reported a short-term benefit, long-term follow-up data are limited. We analyzed the long-term clinical outcomes of autologous bone marrow cell infusion (ABMI) for decompensated liver cirrhosis (LC). Patients enrolled in a pilot single-armed ABMI study were followed up more than 5 years. Bone marrow-derived mononuclear cells (BM-MNCs) from decompensated LC were harvested and after processing were infused into a peripheral vein. The laboratory test results and long-term clinical course including liver transplantation (LT), development of cancer, cause of death, and survival after ABMI were analyzed. Nineteen patients were followed up for a median of 66 months after ABMI. Liver function, including serum levels of albumin and Child–Pugh (CP) score, was improved at the 1-year follow-up. Liver volume was significantly greater, cirrhosis was sustained, and collagen content was decreased at the 6-month follow-up. Five years after ABMI, five patients (26.3%) maintained CP class A without LT or death, and five patients (26.3%) had undergone elective LT. Hepatocellular carcinoma (HCC) occurred in five patients (26.3%), and lymphoma and colon cancer occurred in one patient each. Three patients (15.8%) were lost to follow-up at months 22, 31, and 33, respectively, but maintained CP class A until their last follow-up. Five patients expired due to infection. While improved liver function was maintained in some patients for more than 5 years after ABMI, other patients developed HCC. Further studies of long-term follow-up cohorts after cell therapy for LC are warranted.
Purpose: To evaluate postoperative binocularity after surgical correction of longstanding constant-horizontal adult strabismus without both stereopsis and previous surgery. Methods: Subjects included 43 adults over 18 years of age, who had constant-horizontal strabismus for more than 10 years without previous surgery and stereopsis. The patients were composed of 30 exotropes and 13 esotropes. Patients with a corrected visual acuity less than 20/40 in the deviating eye were excluded. After correcting for refractive error, the angle of deviation was measured, and pre- and postoperative stereopsis was assessed with the Titmus fly test(R) and Randot stereo test. The relationship between duration of deviation and recovery of stereopsis or obtained stereoacuity were evaluated. Results: The mean preoperative angle of deviation was 49.812.56 PD in exotropes and 34.712.41 PD in esotropes. All patients showed suppression of the deviating eye at distance and near before surgery. Postoperatively all patients showed orthophoria within 8 PD. Stereopsis was obtained in 80% of exotropes and in 30.8% of esotropes. The mean postoperative stereoacuity was 449.2815.29 seconds of arc (sec) in exotropes and 10001336.66 sec in esotropes. However, there was no significant relationship between the duration of deviation and the obtained stereoacuity (p>0.05), or between the duration of deviation and the recovery of stereopsis (p>0.05). Conclusions: Adults with longstanding constant-horizontal strabismus more than 10 years obtained stereopsis with good quality after surgical correction. The recovery of stereopsis was much better in exotropes than in esotropes. Recovery was not influenced by the duration of deviation.
Functional screening of novel genes can be efficiently performed by detecting morphological changes of transfected cells. In this study, we developed automated cellular analysis software and found novel genes that induced mitotic phenotypes in transiently transfected HeLa cells. Systemic imaging errors common in high content microscopy were corrected by background subtraction and intensity normalization. Nuclear and chromatin objects were detected by tophat operations. Shape, intensity, and convex-hull features were extracted. Cell types were classified by several logistic regression formulas with 93.9% accuracy in average. The increased % mitotic cells were detected in 47 out of 571 transfected genes. Twenty genes showed more than two-fold increase in % mitotic cells confirmed by manual inspection. Among these, nine genes showed increased tissue expression levels in several tumors, thus, indicating their possible oncogenic roles. These genes will be further investigated biochemically to confirm their cell cycle related functions.
Omission bias occurs when people are more reluctant to accept negative consequences caused by their actions than by their inaction. Recent research on omission bias in decision‐making has found evidence for individual differences, thus indicating that some people are more likely to show omission inclination than others. The present research aims to explore the role of regulatory focus as individual difference variables in omission bias. Moreover, we examine whether anticipated regret mediates the relationship between regulatory focus and moral judgement. Moral judgement tasks utilized include: (i) moral dilemma scenarios (Study 1); and (ii) ethical scenarios embracing apparent legal rule violations (Study 2). The results of both studies show that only prevention focus is significantly related to omission bias in moral judgement. Specifically, this relationship holds regardless of the nature of the ‘omission’ (whether they are deontological or utilitarian). In addition, anticipated regret/guilt for action was found to mediate the relationship between prevention focus and omission bias. Implications and limitations are discussed based on the results of the current study.
// Hyunsoo Cho 1, 2, * , Se Hoon Kim 3, * , Soo-Jeong Kim 1 , Jong Hee Chang 4 , Woo-Ick Yang 3 , Chang-Ok Suh 5 , Yu Ri Kim 1 , Ji Eun Jang 1 , June-Won Cheong 1 , Yoo Hong Min 1 and Jin Seok Kim 1 1 Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea 2 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea 3 Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea 4 Department of Neurosurgery, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea 5 Department of Radiation Oncology, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea * These authors have contributed equally to this work Correspondence to: Jin Seok Kim, email: hemakim@yuhs.ac Keywords: primary central nervous system lymphoma, programmed cell death 1, programmed cell death-ligand 1, programmed cell death-ligand 2, prognosis Received: June 12, 2017 Accepted: July 13, 2017 Published: August 14, 2017 ABSTRACT Programmed cell death 1 (PD-1) and its ligands PD-L1/PD-L2 have been shown to mediate immune evasion in various cancers, but their prognostic implications in patients with primary central nervous system lymphoma (PCNSL) are poorly understood. Therefore, we analyzed 76 PCNSL patients at initial diagnosis who were treated homogenously with high-dose methotrexate-based chemotherapy, and evaluated the prognostic roles of high immunohistochemical PD-1, PD-L1, and PD-L2 expression. The cut-off values for high PD-1 (≥ 70 cells/high power field [HPF]), PD-L1 (≥ 100 cells/HPF), and PD-L2 (≥ 100 cells/HPF) were determined by the area under the receiver operating characteristic curve. Expression of PD-1, PD-L1, and PD-L2 was high in 7.9%, 13.2%, and 42.1% patients, respectively. High PD-1, ( P = 0.007) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic scoring ( P = 0.019) were independently associated with inferior overall survival on multivariate analysis. High PD-1 also remained an independent prognostic factor for inferior progression-free survival ( P = 0.028), as did MSKCC prognostic scoring ( P = 0.041) on multivariate analysis. However, there were no differences in survival according to the expression levels of PD-L1/PD-L2 in PCNSL tumor microenvironment. Our results suggest that PD-1 may be considered a biomarker and potential therapeutic target in PCNSL.
10035 Background: Perioperative Geriatric Comanagement may improve surgical outcomes of older frail cancer patients. We present our 3 year experience with perioperative geriatric comanagement & the electronic Rapid Fitness Assessment (eRFA) at Memorial Hospital (MH). Methods: Since 2015, MH surgical services referred cancer patients age 75+ to the Geriatrics Service for preoperative evaluation including the eRFA (Shahrokni et al, JNCCN, Feb 2017). The eRFA score (0 to 13) is based on 1 point for impairments in the Karnofsky Performance scale score, dependency for basic and instrumental activities of daily living, Timed Up and Go test, history of fall, limited social activity, poor social support, presence of distress, depression, and cognitive impairment, polypharmacy, weight loss, and > 4 comorbid conditions. These patients were then co-managed by the geriatrics and surgical services while hospitalized. We compared the short- and long-term surgical outcomes of frail patients with fit patients. Results: 2291 patients (median age 79) had perioperative geriatric comanagement in 2015-17 with 1175 (51.3%) requiring hospitalization after surgery (average length of stay = 7days). The median eRFA score was 5 (IQR 3-8). 30 day minor & major surgical complications, emegrnecy room visit, readmission & mortality did not differ between frail patients (eRFA > 5) & fit patients (eRFA ≤5) in both the in- and out-patient surgical groups. Among patients requiring hospital stay, frailty was associated with a longer average length of stay (frail vs. fit; 7.7 vs. 6 days, P < 0.001). Frailty was associated with the higher likelihood of dying in 12 months after outpatient surgical procedure (OR = 5.27, p < 0.001) or inpatient surgical procedure (OR = 2.20, p = 0.002). Conclusions: Perioperative comanagement by geriatricians & surgeons leads to similar short term outcomes between frail and fit patients. Future studies should assess the impact of prolonged geriatric comanagement on long-term outcomes of older cancer patients after surgery.
Background: Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe plaque psoriasis. Our prior publication reported significant disease improvement with brodalumab in psoriasis patients who had previously failed treatment with an anti-IL-17A agent.
Objectives: We set out to investigate factors that differed between the patients who had treatment success with brodalumab and those who did not, including disease severity and underlying comorbidities. Other secondary endpoints included the extent of improvement in non-responders, characterization of the patients who discontinued early from the trial, and time to improvement on brodalumab.
Methods: We conducted an Institutional Review Board (IRB)-approved open-label study of a total of 39 subjects enrolled at 3 sites with moderate-to-severe psoriasis. All patients previously failed treatment with an IL-17A agent. Subjects received brodalumab 210 mg via subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks, up to week 16. Subjects were evaluated monthly for improvement in PASI and sPGA.
Results: Of the baseline comorbidities assessed, the only statistically significant difference between responders and non-responders was the presence of higher weight/BMI in non-responders in the AO dataset; this trend disappeared in the NRI dataset. Of the patients that dropped out of the trial early, 3 of the 5 had PASI improvements of >60%. A rapid onset to disease improvement was seen in the trial.
Conclusion: These results indicate that brodalumab may be a good treatment choice for psoriasis patients, including those with severe disease and/or underlying comorbidities.
This study was conducted to develop a population pharmacokinetic (PK) model of methotrexate in Korean patients with haematologic malignancy, identify factors affecting methotrexate PK, and propose an optimal dosage regimen for the Korean population.
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