The prognostic impact of reduced variant burden in elderly patients with acute myeloid leukemia treated with decitabine

Background/Aims@#We evaluated the role of next-generation sequencing (NGS)-based disease monitoring for elderly patients diagnosed with acute myeloid leukemia (AML) who received decitabine therapy. @*Methods@#A total of 123 patients aged > 65 years with AML who received decitabine were eligible. We analyzed the dynamics of variant allele frequency (VAF) in 49 available follow-up samples after the fourth cycle of decitabine. The 58.6% VAF clearance (Δ, [VAF at diagnosis − VAF at follow-up] × 100 / VAF at diagnosis) was the optimal cut-off for predicting overall survival (OS). @*Results@#The overall response rate was 34.1% (eight patients with complete remission [CR], six of CR with incomplete hematologic recovery, 22 with partial responses, and six with morphologic leukemia-free status). Responders (n = 42) had significantly better OS compared with non-responders (n = 42) (median, 15.3 months vs. 6.5 months; p < 0.001). Of the 49 patients available for follow-up targeted NGS analysis, 44 had trackable gene mutations. The median OS of patients with ΔVAF ≥ 58.6% (n=24) was significantly better than that of patients with ΔVAF < 58.6% (n = 19) (20.5 months vs. 9.8 months, p = 0.010). Moreover, responders with ΔVAF ≥ 58.6% (n = 20) had a significantly longer median OS compared with responders with VAF < 58.6% (n = 11) (22.5 months vs. 9.8 months, p = 0.004). @*Conclusions@#This study suggested that combining ΔVAF ≥ 58.6%, a molecular response, with morphologic and hematologic responses can more accurately predict OS in elderly AML patients after decitabine therapy.

Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype. @*Materials and Methods@#Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort. @*Results@#Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838). @*Conclusion@#Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.

Rapid Targeted Sequencing Using Dried Blood Spot Samples for Patients With Suspected Actionable Genetic Diseases

Background@#New genome sequencing technologies with enhanced diagnostic efficiency have emerged. Rapid and timely diagnosis of treatable rare genetic diseases can alter their medical management and clinical course. However, multiple factors, including ethical issues, must be considered. We designed a targeted sequencing platform to avoid ethical issues and reduce the turnaround time. @*Methods@#We designed an automated sequencing platform using dried blood spot samples and a NEOseq_ACTION panel comprising 254 genes associated with Mendelian diseases having curable or manageable treatment options. Retrospective validation was performed using data from 24 genetically and biochemically confirmed patients. Prospective validation was performed using data from 111 patients with suspected actionable genetic diseases. @*Results@#In prospective clinical validation, 13.5% patients presented with medically actionable diseases, including short- or medium-chain acyl-CoA dehydrogenase deficiencies (N=6), hyperphenylalaninemia (N=2), mucopolysaccharidosis type IVA (N=1), alpha thalassemia (N=1), 3-methylcrotonyl-CoA carboxylase 2 deficiency (N=1), propionic acidemia (N=1), glycogen storage disease, type IX(a) (N=1), congenital myasthenic syndrome (N=1), and citrullinemia, type II (N=1). Using the automated analytic pipeline, the turnaround time from blood collection to result reporting was <4 days. @*Conclusions@#This pilot study evaluated the possibility of rapid and timely diagnosis of treatable rare genetic diseases using a panel designed by a multidisciplinary team. The automated analytic pipeline maximized the clinical utility of rapid targeted sequencing for medically actionable genes, providing a strategy for appropriate and timely treatment of rare genetic diseases.

Evolving Indication of Meniscal Allograft Transplantation / 대한정형외과학회잡지

The first human meniscal allograft transplantations (MATs) were performed 30 years ago. In the early era, candidates were limited to patients who have favorable joint conditions. MAT is currently indicated for patients with post-meniscectomy symptoms, such as compartmental pain or effusion after a subtotal or total meniscectomy. The current indication for MAT is being expanded to other patients who were not indicated previously. The present article reviews how the indications of MAT have changed over the years.

Impact of Time Interval between Index Event and Stenting on Periprocedural Risk in Patients with Symptomatic Carotid Stenosis

Objective@#: The purpose of this study was to evaluate the impact of time interval between index event and stenting on the periprocedural risk of stenting for symptomatic carotid stenosis and to determine the optimal timing of stenting. @*Methods@#: This retrospective study included 491 (322 symptomatic [65.6%] and 169 asymptomatic [34.4%]) patients undergoing carotid stenting. The symptomatic patients were categorized into Day 0–3, 4–7, 8–10, 11–14, 15–21, and >21 groups according to the time interval between index event and stenting. Periprocedural (≤30 days) risk for clinical (any neurological deterioration) and radiological (new infarction on postprocedural diffusion-weighted imaging) events of stenting in each time interval versus asymptomatic stenosis was calculated with logistic regression analysis adjusted for confounders, and provided as odds ratio (OR) and 95% confidence interval (CI). @*Results@#: Overall clinical event rate (4.3%) of stenting for symptomatic carotid stenosis was higher than that for asymptomatic stenosis (1.2%; OR, 3.979 [95% CI, 1.093–14.489]; p=0.036). Stenting in Day 0–3 (13.2%; OR, 10.997 [95% CI, 2.333–51.826]; p=0.002) and Day 4–7 (8.3%; OR, 6.775 [95% CI, 1.382–33.227]; p=0.018) was associated with high risk for clinical events. However, the clinical event rates in stenting after 7 days from index event (Day 8–10, 1.8%; Day 11–14, 2.5%; Day 15–21, 0%; Day >21, 2.9%) were not different from that in stenting for asymptomatic stenosis. Overall radiological event rate (55.6%) in symptomatic stenosis was also higher than that in asymptomatic stenosis (35.5%; OR, 2.274 [95% CI, 1.553–3.352]; p21 : 54.8%; OR, 2.203 [95% CI, 1.342–3.641]; p=0.002). @*Conclusion@#: This study showed that as stenting was delayed, the periprocedural risk for clinical events decreased. The clinical event risk was high only in stenting within 7 days and comparable with that for asymptomatic stenosis in stenting after 7 days from index event, although the radiological event risk was not affected by stenting timing. Therefore, our results suggest that delayed stenting after 7 days from symptom onset is a safe strategy for symptomatic stenosis.

Surgery of multiple lymphangioma in small bowel: a rare case report of chronic gastrointestinal bleeding

Small bowel lymphangioma is a rare benign tumor of the lymphatic system, characterized by the presence of dilated lymphatic spaces and significant gastrointestinal bleeding. Small bowel lymphangiomas are rare in adults and case reports are few. Lymphangiomas in the jejunum or ileum are extremely rare and account for less than 1% of all lymphangiomas. The case reported herein is of an older patient (70-year-old male) with melena and chronic anemia (hemoglobin count < 5 g/dL) who had small-sized multiple lymphangiomas in his small bowel (jejunum). Surgical resection was performed after failure of treatment by gastroenteroscopy. Final pathological analysis revealed lymphangioma with thrombus and hemorrhage. After surgery, he no longer had decreased hemoglobin count, nor symptoms of anemia and melena. Also, at the last follow-up visit, the patient's hemoglobin count patient was normal and he returned to normal daily functions.

Clinical outcomes of surgical management for primary gastrointestinal diffuse large B-cell lymphoma: At a single institution experience

PURPOSE: The study aimed to analyze peri/postoperative outcomes and long-term oncologic outcomes after surgical management for primary gastrointestinal diffuse large B-cell lymphoma (DLBL).METHODS: Between January 2001 and December 2013, 19 patients who underwent surgery for primary gastrointestinal DLBL were retrieved from a retrospective database.RESULTS: With a median follow up of 49.2 months, the most common tumor locations were the terminal ileum and cecum (n=14, 73.7%) and stomach (n=4, 21.1%). The most common clinical symptoms were abdominal pain (n=15, 78.9%) and intussusceptions (n=5, 26.3%). None of the patients had B symptoms. Emergency surgery was undertaken in 36.8% (n=7) of the patients. Mean mass size was 8.4 cm; 4 patients (21.1%) had a bulky mass (>10 cm). The International Prognostic Index (IPI) scores were low (n=11, 57.9%), low-intermittent (n=7, 36.8%), and high-intermittent (n=1, 5.3%). Patients' staging was IE (n=9, 47.4%), IIE (n=8, 42.1%), and IVE (n=2, 10.5%) based on the Ann Arbor staging system, and I (n=2, 10.5%), II1 (n=5, 26.4%), IIE (n=10, 52.6%), and IV (n=2, 10.5%) based on the Lugano staging system. B-lymphocyte antigen CD20 was positive in most patients (n=17, 89.5%) and Ki-67 was high (>70%) in 12 patients (63.2%). Two types of chemotherapy were administered: cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (n=5, 26.3%), rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (n=13, 68.4%). The 5-year disease-free survival rate was 94.4% and the 5-year overall survival rate was 89.5%.CONCLUSION: Surgery for primary gastrointestinal DLBL is feasible and acceptable. Low staging of primary gastrointestinal DLBL has good prognosis.

The Influence of Parent and Peer Attachment in Adolescent's Suicidal Ideation: Mediating Effect of Depression and Anxiety / 신경정신의학

OBJECTIVES: The purpose of this study was to investigate the relationships among parent attachment, peer attachment, depression, anxiety, and suicidal ideation of adolescents and the mediating effect of depression and anxiety in these relationships. METHODS: This study targeted 916 middle and high schools students in three different cities. They completed a self-report questionnaire. RESULTS: Parental attachment showed a highly positive correlation with peer attachment while parental attachment and peer attachment showed a highly negative correlation with depression and anxiety. In addition, parental attachment and peer attachment showed a highly negative correlation with suicidal ideation while depression and anxiety showed a highly positive correlation with suicidal ideation. Parental attachment, not only directly, but also indirectly, affects suicidal ideation with mediation of depression and anxiety, indicating that the more secure the level of attachment, the lower the occurrence of depression and anxiety are, which, as a result, can lower suicidal ideation tendency. CONCLUSION: Parent attachment and peer attachment have a direct and indirect effect on suicidal ideation with the mediation of depression and anxiety, which plays a crucial role in suicidal ideation of adolescents.

Re-irradiation of recurrent esophageal cancer after primary definitive radiotherapy

PURPOSE: For recurrent esophageal cancer after primary definitive radiotherapy, no general treatment guidelines are available. We evaluated the toxicities and clinical outcomes of re-irradiation (re-RT) for recurrent esophageal cancer. MATERIALS AND METHODS: We analyzed 10 patients with recurrent esophageal cancer treated with re-RT after primary definitive radiotherapy. The median time interval between primary radiotherapy and re-RT was 15.6 months (range, 4.8 to 36.4 months). The total dose of primary radiotherapy was a median of 50.4 Gy (range, 50.4 to 63.0 Gy). The total dose of re-RT was a median of 46.5 Gy (range, 44.0 to 50.4 Gy). RESULTS: The median follow-up period was 4.9 months (range, 2.6 to 11.4 months). The tumor response at 3 months after the end of re-RT was complete response (n = 2), partial response (n = 1), stable disease (n = 2), and progressive disease (n = 5). Grade 5 tracheoesophageal fistula developed in three patients. The time interval between primary radiotherapy and re-RT was less than 12 months in two of these three patients. Late toxicities included grade 1 dysphagia (n = 1). CONCLUSION: Re-RT of recurrent esophageal cancer after primary radiotherapy can cause severe toxicity.

Eating Attitudes, Depression, Parent-child Interaction, and Family Function of Adolescent Girls / 정신간호학회지

PURPOSE: The purpose of the study was to investigate the prevalence of abnormal eating attitudes and to identify possible risk factors associated with these attitudes among Korean adolescent girls. METHODS: A convenience sample of 1,126 girls aged 15 to 19 years was recruited from thirteen high schools. A self-report survey was conducted including Eating Attitude Test for diagnosing abnormal eating attitudes. Data were analyzed using descriptive statistics and multiple logistic regression with PASW statistics 18.0. RESULTS: Of the participants, 8.3% met the criteria for abnormal eating attitudes. Misperception of body image, depression, and high or low economical status were significantly associated with abnormal eating attitudes (OR=3.50, 95% CI=1.95~6.28; OR=5.47, 95% CI=3.17~9.44; OR=2.26, 95% CI=1.14~4.47; OR=2.41, 95% CI=1.25~4.66). CONCLUSION: The current study identified the family factors as well as internal ones related to abnormal eating attitudes of Korean adolescent girls. The results indicate that the most effective prevention strategies for this population would be to correct their misperception of body image and control depression. Results also suggest that further studies are necessary to develop a predictive model that could explain the influence of family factors including parent-child interaction and family function to abnormal eating attitudes.

Clinical Efficacy Evaluation of Multi-parameter Real-time Polymerase Chain Reaction for the Central Venous Catheter-related Blood Stream Infection / 감염과화학요법

BACKGROUND: The study evaluated the clinical efficacy of a multi-parameter real-time polymerase chain reaction (PCR) test for patients with central venous catheter-related bloodstream infection (CRBSI). MATERIALS AND METHODS: Thirty five patients suspected to have CRBSI were enrolled. The SeptiFast(TM) (SF) multi-parameter real-time PCR test (Roche Diagnostics, Germany) and blood culture were performed and results were compared. RESULTS: The turn-around time for the SF test and blood culture was 32.6+/-28.9 hours and 115.8+/-23.5 hours, respectively. Among the 70 blood samples, the positive rates of SF test and blood culture were 34.3% and 27.1%, respectively, and the agreement rate was 62.9%. Gram-positive bacteria were detected in 10 patients with blood culture and 11 patients with SF test. Gram-negative bacteria were detected in one patient with a blood culture and in seven patients with SF test. Candida was not detected in blood culture but was detected in two patients by the SF test. CONCLUSIONS: SF test was faster and more sensitive for the detection of blood pathogens than blood culture. It provides a more sensitive detection of gram-negative and Candida in blood than does blood culture testing.

A statistical analysis of traumatic emergency patients

No abstract available.