Stroke destroys neurons and their connections leading to focal neurological deficits. Although limited, many patients exhibit a certain degree of spontaneous functional recovery. Structural remodeling of the intracortical axonal connections is implicated in the reorganization of cortical motor representation maps, which is considered to be an underlying mechanism of the improvement in motor function. Therefore, an accurate assessment of intracortical axonal plasticity would be necessary to develop strategies to facilitate functional recovery following a stroke. The present study developed a machine learning-assisted image analysis tool based on multi-voxel pattern analysis in fMRI imaging. Intracortical axons originating from the rostral forelimb area (RFA) were anterogradely traced using biotinylated dextran amine (BDA) following a photothrombotic stroke in the mouse motor cortex. BDA-traced axons were visualized in tangentially sectioned cortical tissues, digitally marked, and converted to pixelated axon density maps. Application of the machine learning algorithm enabled sensitive comparison of the quantitative differences and the precise spatial mapping of the post-stroke axonal reorganization even in the regions with dense axonal projections. Using this method, we observed a substantial extent of the axonal sprouting from the RFA to the premotor cortex and the peri-infarct region caudal to the RFA. Therefore, the machine learningassisted quantitative axonal mapping developed in this study can be utilized to discover intracortical axonal plasticity that may mediate functional restoration following stroke.

Purpose: The objective of this study was to investigate the change in near visual function after the administration of oral silodosin to patients with lower urinary tract symptoms (LUTS). Methods: This prospective study included treatment-naive patients who were scheduled to start treatment with silodosin for LUTS. A comprehensive ophthalmological evaluation including the near vision and the automated pupillometry was performed at baseline and after 3 months of silodosin treatment. For subjective assessment of near visual ability and satisfaction, a Near Activity Visual Questionnaire-10 (NAVQ-10) was also used at the same time (higher scores indicating worse quality). Results: Of 23 patients enrolled in this study, 15 continued with silodosin (8 mg once daily) treatment for 3 months and completed a follow-up evaluation. The mean age of participants was 60.4±8.4 years. Distant visual acuity and spherical error were unchanged after silodosin treatment. However, near vision acuity (logMAR) was improved after treatment (right, 0.47±0.36 vs. 0.38±0.39, P=0.018; left, 0.41±0.37 vs. 0.31±0.34, P=0.068; both, 0.27±0.26 vs. 0.21±0.27, P=0.043). Pupil size under room light decreased significantly in both eyes (right, 3.77±0.60 vs. 3.16±0.58, P=0.001; left, 3.72±0.80 vs. 3.21±0.75, P=0.002). The Rasch scale at NAVQ-10 improved from 54.7±9.9 to 48.5±11.2 (P=0.004). Conclusions This preliminary study demonstrated that highly selective alpha-1A adrenergic receptor antagonists such as silodosin improve near visual acuity and quality in patients with LUTS/benign prostatic hyperplasia. Decrease in pupil size caused by inhibition of adrenergic alpha 1 mediated contraction of iris dilator muscle is a possible mechanism underlying improved near vision.

Background/Aims: Infliximab (IFX) has proven effective as rescue therapy in steroid-refractory acute severe ulcerative colitis (ASUC), however, the long-term real-world data are scarce. Our study aimed to assess the long-term treatment outcomes of IFX in a real-life cohort. Methods: We established a multicenter retrospective cohort of hospitalized patients with ASUC, who met Truelove and Witt’s criteria and received intravenous corticosteroid (IVCS) or IFX during index hospitalization between 2006 and 2016 in 5 university hospitals in Korea. The cohort was systematically followed up until colectomy, death or last follow-up visit. Results: A total of 296 patients were followed up for a mean of 68.9 ± 44.0 months. During index hospitalization, 49 patients were treated with IFX; as rescue therapy for IVCS failure in 37 and as first-line medical therapy for ASUC in 12. All patients treated with IFX avoided colectomy during index hospitalization. The cumulative rates of rehospitalization and colectomy were 20.4% and 6.1% at 3 months and 39.6% and 18.8% at the end of follow-up, respectively. Patients treated with IFX presented with significantly shorter colectomy-free survival than IVCS responders (P= 0.04, log-rank test). Both cytomegalovirus colitis and Clostridioides difficile infection (CDI) were the significant predictors of colectomy in the overall study cohort (hazard ratios of 6.57 and 4.61, respectively). There were no fatalities. Conclusions Our real-world cohort study demonstrated that IFX is an effective therapeutic option in Korean patients with ASUC, irrespective of IFX indication. Aggressive vigilance for cytomegalovirus colitis and CDI is warranted for hospitalized patients with ASUC.

Purpose: The objective of this study was to investigate the change in near visual function after the administration of oral silodosin to patients with lower urinary tract symptoms (LUTS). Methods: This prospective study included treatment-naive patients who were scheduled to start treatment with silodosin for LUTS. A comprehensive ophthalmological evaluation including the near vision and the automated pupillometry was performed at baseline and after 3 months of silodosin treatment. For subjective assessment of near visual ability and satisfaction, a Near Activity Visual Questionnaire-10 (NAVQ-10) was also used at the same time (higher scores indicating worse quality). Results: Of 23 patients enrolled in this study, 15 continued with silodosin (8 mg once daily) treatment for 3 months and completed a follow-up evaluation. The mean age of participants was 60.4±8.4 years. Distant visual acuity and spherical error were unchanged after silodosin treatment. However, near vision acuity (logMAR) was improved after treatment (right, 0.47±0.36 vs. 0.38±0.39, P=0.018; left, 0.41±0.37 vs. 0.31±0.34, P=0.068; both, 0.27±0.26 vs. 0.21±0.27, P=0.043). Pupil size under room light decreased significantly in both eyes (right, 3.77±0.60 vs. 3.16±0.58, P=0.001; left, 3.72±0.80 vs. 3.21±0.75, P=0.002). The Rasch scale at NAVQ-10 improved from 54.7±9.9 to 48.5±11.2 (P=0.004). Conclusions This preliminary study demonstrated that highly selective alpha-1A adrenergic receptor antagonists such as silodosin improve near visual acuity and quality in patients with LUTS/benign prostatic hyperplasia. Decrease in pupil size caused by inhibition of adrenergic alpha 1 mediated contraction of iris dilator muscle is a possible mechanism underlying improved near vision.

Background/Aims: Infliximab (IFX) has proven effective as rescue therapy in steroid-refractory acute severe ulcerative colitis (ASUC), however, the long-term real-world data are scarce. Our study aimed to assess the long-term treatment outcomes of IFX in a real-life cohort. Methods: We established a multicenter retrospective cohort of hospitalized patients with ASUC, who met Truelove and Witt’s criteria and received intravenous corticosteroid (IVCS) or IFX during index hospitalization between 2006 and 2016 in 5 university hospitals in Korea. The cohort was systematically followed up until colectomy, death or last follow-up visit. Results: A total of 296 patients were followed up for a mean of 68.9 ± 44.0 months. During index hospitalization, 49 patients were treated with IFX; as rescue therapy for IVCS failure in 37 and as first-line medical therapy for ASUC in 12. All patients treated with IFX avoided colectomy during index hospitalization. The cumulative rates of rehospitalization and colectomy were 20.4% and 6.1% at 3 months and 39.6% and 18.8% at the end of follow-up, respectively. Patients treated with IFX presented with significantly shorter colectomy-free survival than IVCS responders (P= 0.04, log-rank test). Both cytomegalovirus colitis and Clostridioides difficile infection (CDI) were the significant predictors of colectomy in the overall study cohort (hazard ratios of 6.57 and 4.61, respectively). There were no fatalities. Conclusions Our real-world cohort study demonstrated that IFX is an effective therapeutic option in Korean patients with ASUC, irrespective of IFX indication. Aggressive vigilance for cytomegalovirus colitis and CDI is warranted for hospitalized patients with ASUC.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days –8 to –5), and the target area under the curve was 75,000 µg·hr/L. Fludarabine (40 mg/m2) was administered once daily for 6 consecutive days from days –8 to –3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days –4 to –2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.
Antilymphocyte Serum ; Bone Marrow Transplantation* ; Bone Marrow* ; Busulfan* ; Granulomatous Disease, Chronic* ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Transplantation Conditioning

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Several recent findings that there are activating mutations in the KIT and PDGFRA (platelet-derived growth factor receptor-alpha) genes of GISTs provide the rationale for using targeted therapies such as imatinib or sunitinib. Sunitinib, an oral multitargeted receptor tyrosine kinase inhibitor that inhibits kinases such as KIT, PDGFR (platelet-derived growth factor recepter), and VEGFR (vascular endothelial growth factor receptor), was recently approved for the treatment of imatinib-refractory GIST. Sunitinib is generally well tolerated and has an acceptable toxicity profile; an adverse event such as bowel perforation is rare. We present a patient with imatinib-refractory GIST who was successfully treated using sunitinib, but developed bowel perforation. The mechanism involved in bowel perforation associated with sunitinib is unknown. However, we presume that in our patient, the dramatic reduction in disseminated peritoneal metastases and bowel invasion of recurrent GIST during sunitinib treatment might have resulted in the bowel perforation.
Endothelial Growth Factors ; Gastrointestinal Stromal Tumors* ; Gastrointestinal Tract ; Humans ; Intestinal Perforation ; Neoplasm Metastasis ; Phosphotransferases ; Protein-Tyrosine Kinases ; Imatinib Mesylate

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Several recent findings that there are activating mutations in the KIT and PDGFRA (platelet-derived growth factor receptor-alpha) genes of GISTs provide the rationale for using targeted therapies such as imatinib or sunitinib. Sunitinib, an oral multitargeted receptor tyrosine kinase inhibitor that inhibits kinases such as KIT, PDGFR (platelet-derived growth factor recepter), and VEGFR (vascular endothelial growth factor receptor), was recently approved for the treatment of imatinib-refractory GIST. Sunitinib is generally well tolerated and has an acceptable toxicity profile; an adverse event such as bowel perforation is rare. We present a patient with imatinib-refractory GIST who was successfully treated using sunitinib, but developed bowel perforation. The mechanism involved in bowel perforation associated with sunitinib is unknown. However, we presume that in our patient, the dramatic reduction in disseminated peritoneal metastases and bowel invasion of recurrent GIST during sunitinib treatment might have resulted in the bowel perforation.
Endothelial Growth Factors ; Gastrointestinal Stromal Tumors* ; Gastrointestinal Tract ; Humans ; Intestinal Perforation ; Neoplasm Metastasis ; Phosphotransferases ; Protein-Tyrosine Kinases ; Imatinib Mesylate

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.
African Americans/genetics ; Alleles ; Amino Acids/metabolism ; Asian Continental Ancestry Group/genetics ; Dihydrouracil Dehydrogenase (NADP)/*genetics ; Ethnic Groups/*genetics ; European Continental Ancestry Group/genetics ; Fluorouracil/metabolism ; Gene Frequency ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.
African Americans/genetics ; Alleles ; Amino Acids/metabolism ; Asian Continental Ancestry Group/genetics ; Dihydrouracil Dehydrogenase (NADP)/*genetics ; Ethnic Groups/*genetics ; European Continental Ancestry Group/genetics ; Fluorouracil/metabolism ; Gene Frequency ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA