Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

The brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroprotection, and we have previously demonstrated BDNF-mediated neuroprotective effects in mesenchymal stromal cells (MSCs). The present study aimed to investigate whether BDNF-overexpressing MSCs enhance the therapeutic efficacy of naïve MSCs in a preclinical model of severe neonatal intraventricular hemorrhage (IVH). We exposed primary rat neuronal cells to 40 U of thrombin overnight in vitro. Subsequently, the neuronal cells were co-cultured with either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 1 mL media) for 24 hours. Next, 300 μL of maternal blood was injected into bilateral ventricles on postnatal day (P)4 to induce severe IVH in newborn Sprague-Dawley male rats. At P6, either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 10 μL saline) were transplanted intraventricularly. Behavioral function tests, including passive avoidance, followed by endpoint analyses of brain tissue and cerebrospinal fluid were performed at P35. BDNF-overexpressing MSCs enhanced the effects of naïve MSCs against cell death, cytotoxicity, and oxidative stress in vitro. Notably, naïve and BDNF-overexpressing MSCs did not attenuate post-hemorrhagic ventricular dilatation, neuronal cell death, or gliosis. However, BDNF-overexpressing MSCs attenuated microglial activation.Furthermore, inflammatory cytokine (interleukin [IL]-1α, IL-1β, IL-6, and tumor necrosis factor-α) levels and memory function assessed using a passive avoidance test significantly improved in the BDNF-overexpressing MSC transplanted group compared with the naïve MSC transplanted group. Our data suggest that BDNF-overexpressing MSCs may offer superior protective effects to naïve MSCs in a neonatal IVH model.

Sarcopenia is common in hemodialysis patients. This study aimed to evaluate the effect of simultaneous nutritional support and intradialytic neuromuscular electrical stimulation (NMES) in hemodialysis patients. Methods: We performed a 12-week, multicenter, randomized controlled trial. The participants were randomly assigned to the control group, the protein group (25 g of protein at every dialysis session), the NMES group (intradialytic NMES to quadriceps femoris muscles), and the NMES + P group (NMES with protein supplementation). The primary outcome was the difference in hand grip strength (HGS) and leg muscle strength (LMS) among groups. Secondary outcomes included body composition, physical performance (the 10-m walk test and the timed up and go test [TUG]), and questionnaires about quality of life (QoL), physical activity, and depression. In addition, subgroup analysis was performed by dividing NMES and NMES + P groups into high- and low-intensity NMES groups. Results: Fifty-nine patients completed all the study outcomes. There was no difference in muscle strength (HGS and LMS) and muscle mass among groups. Gait speed improved in NMES and NMES + P groups. Subscale scores for QoL (kidney disease effect, role limitations due to physical or emotional problems, and overall health ratings) improved in the NMES + P group. In subgroup analysis, LMS and TUG improved only in the high-intensity NMES group. Conclusion: In this study, NMES and-/or- protein supplementation did not make a significant difference in HGS and LMS. However, NMES or NMES + P improved functional capacity and QoL. Furthermore, higher NMES was superior in improving LMS and functional capacity.

Holoprosencephaly (HPE) is a rare congenital disorder characterized by the incomplete separation of the prosencephalon. The clinical spectrum of HPE depends on the subtypes observed on imaging, which includes lobar, semilobar, and alobar variants. Cyclopia, the most severe form of alobar HPE, is typically associated with early postnatal death within a few days. We report the case of a female infant was born at 38 weeks and 6 days of gestation, weighing 2,410 g, to a 39-year-old mother via vaginal delivery. She was the second baby of dichorionic-diamniotic twins. The neonate was born with multiple defects including facial anomalies such as cyclopia and arrhinia and was diagnosed with alobar HPE with cyclopia. This condition was suspected prenatally at 17 weeks of gestation and confirmed postnatally using brain magnetic resonance imaging. The cause of death in our patient was aspiration pneumonia with aggravated central apnea, and she survived for 8 months (240 days) with comfort care alone, without aggressive life support. This is the first report of an infant with alobar HPE, cyclopia, and arrhinia surviving for 240 days with only comfort care, marking the longest documented survival for this typically lethal condition without invasive interventions.

Holoprosencephaly (HPE) is a rare congenital disorder characterized by the incomplete separation of the prosencephalon. The clinical spectrum of HPE depends on the subtypes observed on imaging, which includes lobar, semilobar, and alobar variants. Cyclopia, the most severe form of alobar HPE, is typically associated with early postnatal death within a few days. We report the case of a female infant was born at 38 weeks and 6 days of gestation, weighing 2,410 g, to a 39-year-old mother via vaginal delivery. She was the second baby of dichorionic-diamniotic twins. The neonate was born with multiple defects including facial anomalies such as cyclopia and arrhinia and was diagnosed with alobar HPE with cyclopia. This condition was suspected prenatally at 17 weeks of gestation and confirmed postnatally using brain magnetic resonance imaging. The cause of death in our patient was aspiration pneumonia with aggravated central apnea, and she survived for 8 months (240 days) with comfort care alone, without aggressive life support. This is the first report of an infant with alobar HPE, cyclopia, and arrhinia surviving for 240 days with only comfort care, marking the longest documented survival for this typically lethal condition without invasive interventions.

Holoprosencephaly (HPE) is a rare congenital disorder characterized by the incomplete separation of the prosencephalon. The clinical spectrum of HPE depends on the subtypes observed on imaging, which includes lobar, semilobar, and alobar variants. Cyclopia, the most severe form of alobar HPE, is typically associated with early postnatal death within a few days. We report the case of a female infant was born at 38 weeks and 6 days of gestation, weighing 2,410 g, to a 39-year-old mother via vaginal delivery. She was the second baby of dichorionic-diamniotic twins. The neonate was born with multiple defects including facial anomalies such as cyclopia and arrhinia and was diagnosed with alobar HPE with cyclopia. This condition was suspected prenatally at 17 weeks of gestation and confirmed postnatally using brain magnetic resonance imaging. The cause of death in our patient was aspiration pneumonia with aggravated central apnea, and she survived for 8 months (240 days) with comfort care alone, without aggressive life support. This is the first report of an infant with alobar HPE, cyclopia, and arrhinia surviving for 240 days with only comfort care, marking the longest documented survival for this typically lethal condition without invasive interventions.

Holoprosencephaly (HPE) is a rare congenital disorder characterized by the incomplete separation of the prosencephalon. The clinical spectrum of HPE depends on the subtypes observed on imaging, which includes lobar, semilobar, and alobar variants. Cyclopia, the most severe form of alobar HPE, is typically associated with early postnatal death within a few days. We report the case of a female infant was born at 38 weeks and 6 days of gestation, weighing 2,410 g, to a 39-year-old mother via vaginal delivery. She was the second baby of dichorionic-diamniotic twins. The neonate was born with multiple defects including facial anomalies such as cyclopia and arrhinia and was diagnosed with alobar HPE with cyclopia. This condition was suspected prenatally at 17 weeks of gestation and confirmed postnatally using brain magnetic resonance imaging. The cause of death in our patient was aspiration pneumonia with aggravated central apnea, and she survived for 8 months (240 days) with comfort care alone, without aggressive life support. This is the first report of an infant with alobar HPE, cyclopia, and arrhinia surviving for 240 days with only comfort care, marking the longest documented survival for this typically lethal condition without invasive interventions.

Holoprosencephaly (HPE) is a rare congenital disorder characterized by the incomplete separation of the prosencephalon. The clinical spectrum of HPE depends on the subtypes observed on imaging, which includes lobar, semilobar, and alobar variants. Cyclopia, the most severe form of alobar HPE, is typically associated with early postnatal death within a few days. We report the case of a female infant was born at 38 weeks and 6 days of gestation, weighing 2,410 g, to a 39-year-old mother via vaginal delivery. She was the second baby of dichorionic-diamniotic twins. The neonate was born with multiple defects including facial anomalies such as cyclopia and arrhinia and was diagnosed with alobar HPE with cyclopia. This condition was suspected prenatally at 17 weeks of gestation and confirmed postnatally using brain magnetic resonance imaging. The cause of death in our patient was aspiration pneumonia with aggravated central apnea, and she survived for 8 months (240 days) with comfort care alone, without aggressive life support. This is the first report of an infant with alobar HPE, cyclopia, and arrhinia surviving for 240 days with only comfort care, marking the longest documented survival for this typically lethal condition without invasive interventions.

Background/Aims: The recent update on Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added a decrease in fecal calprotectin (FC) to an acceptable range as an intermediate target for Crohn’s disease (CD). We aimed to investigate whether postinduction FC could predict future persistent remission (PR) and endoscopic healing (EH) after 1 year of treatment with infliximab (IFX) in pediatric patients with CD. Methods: This multicenter retrospective observational study included pediatric patients with CD who were followed up for at least 1 year after starting IFX. The association of postinduction FC with PR and EH was investigated. Results: A total of 132 patients were included in this study. PR and EH were observed in 71.2% (94/132) and 73.9% (82/111) of the patients, respectively. In multivariate logistic regression analysis, only the postinduction FC level was associated with PR (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08 to 0.66; p=0.009). The FC levels at initiation of IFX and postinduction were significantly associated with EH (OR, 0.73; 95% CI, 0.53 to 0.99; p=0.044 and OR, 0.20; 95% CI, 0.06 to 0.49; p=0.002, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level for postinduction FC associated with PR was 122 mg/kg, and that associated with EH was 377 mg/kg. Conclusions Postinduction FC was associated with PR and EH after 1 year of treatment with IFX in pediatric patients with CD. Our findings emphasize the importance of FC as an intermediate target in the treat-to-target era.

Objective: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). Materials and Methods: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm 2 was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive.The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). Results: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4–79.9), 90.8% (95% CI: 85.6–94.2), and 83.5% (95% CI: 78.6–87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8–97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9–89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1–79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52–0.63) before training and 0.68 (95% CI: 0.62–0.74) after training, with a difference of 0.11 (95% CI: 0.02–0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69–0.74) before training and 0.79 (95% CI: 0.76–0.80) after training (P = 0.002). Conclusion Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.