Purpose: This study aimed to develop a model for predicting pathologic extracapsular extension (ECE) and seminal vesicle invasion (SVI) while integrating magnetic resonance imaging-based T-staging (cTMRI, cT1c-cT3b). Materials and Methods: A total of 1,915 who underwent radical prostatectomy between 2006-2016 met the inclusion/exclusion criteria. We performed a multivariate logistic regression analysis as well as Bayesian network (BN) modeling based on possible confounding factors. The BN model was internally validated using 5-fold validation. Results: According to the multivariate logistic regression analysis, initial prostate-specific antigen (iPSA) (β=0.050, p < 0.001), percentage of positive biopsy cores (PPC) (β=0.033, p < 0.001), both lobe involvement on biopsy (β=0.359, p=0.009), Gleason score (β=0.358, p < 0.001), and cTMRI (β=0.259, p < 0.001) were significant factors for ECE. For SVI, iPSA (β=0.037, p < 0.001), PPC (β=0.024, p < 0.001), Gleason score (β=0.753, p < 0.001), and cTMRI (β=0.507, p < 0.001) showed statistical significance. BN models to predict ECE and SVI were also successfully established. The overall area under the receiver operating characteristic curve (AUC)/accuracy of the BN models were 0.76/73.0% and 0.88/89.6% for ECE and SVI, respectively. According to internal comparison between the BN model and Roach formula, BN model had improved AUC values for predicting ECE (0.76 vs. 0.74, p=0.060) and SVI (0.88 vs. 0.84, p < 0.001). Conclusion Two models to predict pathologic ECE and SVI integrating cTMRI were established and installed on a separate website for public access to guide radiation oncologists.

Proximal junctional problems are among the potential complications of surgery for adult spinal deformity (ASD) and are associated with higher morbidity and increased rates of revision surgery. The diverse manifestations of proximal junctional problems range from proximal junctional kyphosis (PJK) to proximal junctional failure (PJF). Although there is no universally accepted definition for PJK, the most common is a proximal junctional angle greater than 10° that is at least 10° greater than the preoperative measurement. PJF represents a progression from PJK and is characterized by pain, gait disturbances, and neurological deficits. The risk factors for PJK can be classified according to patient-related, radiological, and surgical factors. Based on an understanding of the modifiable factors that contribute to reducing the risk of PJK, prevention strategies are critical for patients with ASD.

Background: Conventional diagnosis of fragile X syndrome (FXS) is based on a combination of fragment analysis (FA) and Southern blotting (SB); however, this diagnostic approach is time- and labor-intensive and has pitfalls such as the possibility of missing large number alleles. Triplet repeat primed PCR (TP-PCR) is a current alternative used to overcome these limitations. We evaluated the diagnostic usefulness of TP-PCR compared with the conventional diagnostic protocol consisting of FA and/or SB in terms of allele categorization, repeat number correlation, and zygosity concordance in female genetic carriers. Methods: From November 2013 to March 2018, 458 patients (326 males, 132 females) were simultaneously examined using FA and/or SB and TP-PCR by detecting CGG repeat numbers in FMR gene and diagnosed as per American College of Medical Genetics guidelines. Results: The TP-PCR results showed high concordance with the FA and/or SB results for all three aspects (allele categorization, repeat number correlation, and zygosity concordance in female genetic carriers). TP-PCR detected CGG expansions ≥ 200 in all full mutation (FM) allele cases in male patients, as well as both the normal allele (NL) and FM allele in female carriers. In premutation (PM) allele carriers, the TP-PCR results were consistent with the FA and/or SB results. In terms of zygosity concordance in female genetic carriers, 12 NL cases detected by TP-PCR showed a merged peak consisting of two close heterozygous peaks; however, this issue was resolved using a 10-fold dilution. Conclusions TP-PCR may serve as a reliable alternative method for FXS diagnosis.

Background/Aims: Understanding leukemic stem cell (LSC) is important for acute myeloid leukemia (AML) treatment. However, association of LSC with patient prognosis and genetic information in AML patients is unclear. Methods: Here we investigated the associations between genetic information and the various LSC phenotypes, namely multipotent progenitor (MPP)-like, lymphoid primed multipotent progenitor (LMPP)-like and granulocyte-macrophage progenitors (GMP)-like LSC in 52 AML patients. Results: In secondary AML patients, MPP-like LSC was significantly higher than de novo AML (p = 0.0037). The proportion of MPP-like LSC was especially high in post-myeloproliferative neoplasm AML (p = 0.0485). There was no correlation between age and LSC phenotype. Mutations of KRAS and NRAS were observed in MPP-like LSC dominant patients, TP53 and ASXL1 mutations in LMPP-like LSC dominant patients, and CEBPA, DNMT3A and IDH1 mutations in GMP-like LSC dominant patients. Furthermore, KRAS mutation was significantly associated with MPP-like LSC expression (p = 0.0540), and TP53 mutation with LMPP-like LSC expression (p = 0.0276). When the patients were separated according to the combined risk including next generation sequencing data, the poorer the prognosis, the higher the LMPP-like LSC expression (p = 0.0052). This suggests that the dominant phenotype of LSC is one of the important factors in predicting the prognosis and treatment of AML. Conclusions LSC phenotype in AML is closely associated with the recurrent mutations which has prognostic implication. Further research to confirm the meaning of LSC phenotype in the context of genetic aberration is warranted.

Objective: To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies. Methods: We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose. Results: Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed. Conclusion Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.

Thalassemia is characterized by the impaired synthesis of globin chains due to disease-causing variants in α- or β-globin genes. In this review, we provide an overview of the molecular basis underlying α- and β-thalassemia, and of the current technologies used to characterize these disease-causing variants for the diagnosis of thalassemia.Understanding these molecular basis and technologies will prove to be beneficial for the accurate diagnosis of thalassemia.

Background: Endoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes. Methods: Medical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and LundMackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes. Results: In total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [−0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) − 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed. Conclusion Tissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS.

Objective: To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies. Methods: We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose. Results: Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed. Conclusion Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.

Thalassemia is characterized by the impaired synthesis of globin chains due to disease-causing variants in α- or β-globin genes. In this review, we provide an overview of the molecular basis underlying α- and β-thalassemia, and of the current technologies used to characterize these disease-causing variants for the diagnosis of thalassemia.Understanding these molecular basis and technologies will prove to be beneficial for the accurate diagnosis of thalassemia.