Current status of pediatric umbilical cord blood transplantation in Korea: a multicenter retrospective analysis of 236 cases

We report the outcome of 236 pediatric umbilical cord blood transplantations (UCBT) performed in Korea. Given that the sources of the grafts were mostly unrelated donors (n = 226; 95.8%), only the results of unrelated UCBT were included for all statistics. The most frequent primary disease was acute leukemia (n = 167). In total, 91.7% of recipients were seropositive for cytomegalovirus (CMV). The median doses of nucleated cells and CD34+ cells were 4.84 × 10(7)/kg and 2.00 × 10(5)/kg, respectively. The median times to neutrophil (>0.5 × 10(9)/L) and platelet recovery (>20 × 10(9)/L) were 18 and 45 days, respectively. Grade 2-4 acute graft-versus-host-disease (GVHD) and chronic GVHD developed in 41.1 and 36.1% of cases, respectively. Forty-five patients developed CMV disease. The 5-year overall and event-free survival were 47.5 and 36.9%, respectively. Multivariate analysis revealed that adverse factors for survival of the whole cohort were total body irradiation-based conditioning (P = 0.007), salvage transplant (P = 0.001), failure to achieve early complete chimerism (P < 0.0005), and CMV disease (P = 0.001). The outcomes of the single- and double-unit UCBT (n = 64) were similar, while double-unit recipients were heavier (P < 0.0005) and older (P < 0.0005). We conclude that double-unit UCBT is a reasonable option for older or heavier children and that the thorough surveillance of CMV infection and the development of an effective CMV therapeutic strategy may be especially important for Korean children, whose CMV seroprevalence exceeds 90%.     

Prognostic significance of adverse events associated with preoperative radiotherapy for rectal cancer

Purpose

Adverse events may occur in patients receiving preoperative radiotherapy (PRT) for rectal cancers. The aim of this study is to clarify the clinical and pathological features of the patients with PRT-related adverse events, and the significance of the adverse events on the clinical outcome.

Methods

Seventy-five patients with T3 or T4 low rectal cancers curatively resected following PRT were studied. Thirty-one patients received radiotherapy, and 44 patients received chemoradiotherapy with tegafur-uracil and leucovorin. The total radiation dose was 50?C50.4?Gy given in 25?C28 fractions and the operation was performed 4?C8?weeks after PRT. PRT-related adverse events were graded in accordance with the Common Terminology Criteria for Adverse Events v3.0.

Results

The most frequent adverse events were leukocytopenia and diarrhea, observed in 12% and 24% of patients, respectively. The majority of the leukocytopenia and diarrhea was grade 1?C2 toxicity. Women experienced leukocytopenia more frequently than men (28% vs. 7%, p?=?0.0317); however, no other predisposing factor for adverse events was recognized. Patients with leukocytopenia or diarrhea showed a better 5-year relapse-free survival rate than those without (94?±?5% vs. 49?±?9%, p?=?0.00054), and the presence of these adverse events was an independent prognostic factor in a multivariate analysis.

Conclusions

The presence of leukocytopenia or diarrhea was an independent predictor of a fair prognosis after curative operation following PRT, and thus these adverse events seem not to discourage oncologists and patients from considering PRT for rectal cancers.     

Practical development and operationalization of a 12-hour hospital census prediction algorithm

Hospital census prediction has well-described implications for efficient hospital resource utilization, and recent issues with hospital crowding due to CoVID-19 have emphasized the importance of this task. Our team has been leading an institutional effort to develop machine-learning models that can predict hospital census 12 hours into the future. We describe our efforts at developing accurate empirical models for this task. Ultimately, with limited resources and time, we were able to develop simple yet useful models for 12-hour census prediction and design a dashboard application to display this output to our hospital’s decision-makers. Specifically, we found that linear models with ElasticNet regularization performed well for this task with relative 95% error of +/− 3.4% and that this work could be completed in approximately 7 months.     

Symptom structure of antipsychotic-induced obsessive compulsive symptoms in schizophrenia patients

Objective

The use of clozapine or other second generation antipsychotics (SGAs) has been reported to produce obsessive compulsive (OC) symptoms as adverse mental affects. However, it is not yet clear if SGA-induced OC symptoms have the same phenomenological characteristics as those displayed in obsessive compulsive disorder (OCD). This study investigated the nature of symptoms and dimensions of SGA-induced OC symptoms in schizophrenia patients, which were then compared with those reported in pure OCD.

Methods

The study subjects were fifty-one schizophrenia patients with SGA-induced OC symptoms. Symptom evaluation was performed using the Korean version of the Yale–Brown Obsessive Compulsive Scale (Y-BOCS). Exploratory factor analysis of symptom categories of Y-BOCS symptom checklist (Y-BOCS-SC) was conducted.

Results

Frequencies of individual symptom categories were comparable to those reported in Korean OCD patients. Five factors (forbidden thoughts, hoarding, cleaning, symmetry, and counting) were generated from 13 main symptom categories, which accounted for 70.7% of the total variance. This factor structure is also remarkably similar to those reported in pure OCD patients. The factor score of ‘cleaning’ was significantly correlated with the overall severity of OC symptoms (P < 0.01).

Conclusion

A high level of similarity between the nature of symptoms and dimensions identified in patients with SGA-induced OC symptoms and those revealed in OCD patients suggests a common biological mechanism underlying these two clinical conditions.     

Age-dependent neurovascular abnormalities and altered microglial morphology in the YAC128 mouse model of Huntington disease

Central nervous system (CNS) inflammatory processes including microglial activation have been implicated in the pathogenesis of neurodegenerative diseases such as Huntington Disease (HD). We report age-dependent changes in striatal microglial morphology and vasculature in the YAC128 mouse model of HD. Decreases in microglial ramification along with a decrease in vessel diameter and increased vessel density and length suggest the presence of microgliosis and proangiogenic activity in YAC128 mice. Our hypothesis for this study was that the changes in microglial morphology and perturbations in vasculature may be involved in the pathogenesis of HD and that peripheral challenge with the bacterial endotoxin, lipopolysaccharide (LPS), will exacerbate these microglial and vascular changes as well as the HD phenotype in YAC128 mice at 12 months. Chronic peripheral LPS (1 mg/kg) potentiated microglial activation indicated by an increase in microglial cell body size and retraction of processes. This potentiation in microglial activation with chronic peripheral LPS challenge was paralleled with vascular remodeling including dilatation, increased vessel wall thickness, increased BBB permeability and fibrinogen deposition in YAC128 striatum. Although peripheral LPS caused an increase in microglial activation and degenerative changes in cerebrovasculature, the phenotypic hallmarks of HD in YAC128 mice such as motor coordination deficits and decreased striatal volume were not exacerbated by chronic peripheral LPS exposure. This study identifies age-dependent increases in microglial activation and angiogenesis in YAC128 at 12 months. Peripheral inflammation induced by chronic LPS causes similar changes but does not influence the HD phenotype in YAC128 mice.