Purpose: We aimed to investigate how genetic predisposition to drinking and gastric cancer (GC) modifies the association between alcohol consumption and GC risk in the Korean population. Materials and Methods: Polygenic risk scores for GC (PRS-GC) and alcohol consumption (PRS-Alcohol) were formulated using genome-wide association results from BioBank Japan. Validation was performed using Korean cohorts (SNUBH-GENIE cohort), incorporating 8,846 controls and 531 patients with GC. Subsequently, these PRSs were applied to an independent Korean cohort of 67,771 participants, including 313 patients with GC during the follow-up for 14 years (KoGES cohort). Results: In KoGES cohort, the influence of alcohol consumption on GC risk was significantly altered by the PRS-GC and exhibited a synergistic interaction effect. PRS-Alcohol itself shows a negative correlation with GC risk. However, when actual alcohol consumption significantly exceeded genetically predicted levels, the risk of alcohol-related GC was notably increased (adjusted hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.72). Heavy drinkers in the high–PRS-GC/low–PRS-Alcohol group had a 2.16 times higher risk of GC than non-to-light drinkers, which was prominent in males. Conclusion Korean drinkers with higher PRS-GC who consume alcohol more than genetically predicted levels are susceptible to GC. PRS-GC and PRS-Alcohol may be beneficial for assessing the impact of alcohol consumption on GC risk in Koreans.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

Background: This study aimed to estimate the association between mRNA coronavirus disease 2019 (COVID-19) vaccine exposure during pregnancy and the risks of preterm birth and congenital malformations leveraging a national population data. Methods: This retrospective cohort study utilized national data from the National Health Insurance System, linking maternal and infant records with COVID-19 vaccination registries.Newborns with congenital malformations were identified using diagnosis codes. The analysis included women aged 20–49 who gave live births between February 2022 and December 2022. Odds ratios (ORs) for preterm birth and any congenital malformation per COVID-19 vaccination during pregnancy compared to 1:4 matched unvaccinated controls, adjusted for maternal age, residential area, employment, income, disability, month of conception, prepregnancy obesity, smoking, and severe acute respiratory syndrome coronavirus 2 infection prior to pregnancy, were calculated. We compared the risk of two outcomes between BNT162b2 and mRNA-1273. Results: Among 106,692 women who gave birth during the study period, 8,966 (8.4%) received a COVID-19 vaccination during pregnancy. Of the newborns, 7,039 (6.6%) were preterm births and 7,658 (7.2%) had congenital malformations. COVID-19 vaccination during pregnancy was associated with a comparable risk of preterm birth (OR, 1.03; 95% confidence interval [CI], 0.77–1.36) and a similar risk of congenital malformations (0.90; 95% CI, 0.72–1.12) compared to non-vaccinees. The ORs of preterm birth (1.02; 95% CI, 0.77–1.36) and congenital malformation (0.91; 95% CI, 0.73–1.14) for mRNA-1273 were comparable to those for BNT162b2. Conclusion COVID-19 vaccines during pregnancy poses no increased risk of preterm birth and congenital malformations compared to those not exposed to the vaccine, with similar risk levels observed between the two mRNA vaccines. This finding provides additional evidence supporting the safety of COVID-19 vaccines.

Background: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Background: This study aimed to estimate the association between mRNA coronavirus disease 2019 (COVID-19) vaccine exposure during pregnancy and the risks of preterm birth and congenital malformations leveraging a national population data. Methods: This retrospective cohort study utilized national data from the National Health Insurance System, linking maternal and infant records with COVID-19 vaccination registries.Newborns with congenital malformations were identified using diagnosis codes. The analysis included women aged 20–49 who gave live births between February 2022 and December 2022. Odds ratios (ORs) for preterm birth and any congenital malformation per COVID-19 vaccination during pregnancy compared to 1:4 matched unvaccinated controls, adjusted for maternal age, residential area, employment, income, disability, month of conception, prepregnancy obesity, smoking, and severe acute respiratory syndrome coronavirus 2 infection prior to pregnancy, were calculated. We compared the risk of two outcomes between BNT162b2 and mRNA-1273. Results: Among 106,692 women who gave birth during the study period, 8,966 (8.4%) received a COVID-19 vaccination during pregnancy. Of the newborns, 7,039 (6.6%) were preterm births and 7,658 (7.2%) had congenital malformations. COVID-19 vaccination during pregnancy was associated with a comparable risk of preterm birth (OR, 1.03; 95% confidence interval [CI], 0.77–1.36) and a similar risk of congenital malformations (0.90; 95% CI, 0.72–1.12) compared to non-vaccinees. The ORs of preterm birth (1.02; 95% CI, 0.77–1.36) and congenital malformation (0.91; 95% CI, 0.73–1.14) for mRNA-1273 were comparable to those for BNT162b2. Conclusion COVID-19 vaccines during pregnancy poses no increased risk of preterm birth and congenital malformations compared to those not exposed to the vaccine, with similar risk levels observed between the two mRNA vaccines. This finding provides additional evidence supporting the safety of COVID-19 vaccines.

Background: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

Background: This study aimed to estimate the association between mRNA coronavirus disease 2019 (COVID-19) vaccine exposure during pregnancy and the risks of preterm birth and congenital malformations leveraging a national population data. Methods: This retrospective cohort study utilized national data from the National Health Insurance System, linking maternal and infant records with COVID-19 vaccination registries.Newborns with congenital malformations were identified using diagnosis codes. The analysis included women aged 20–49 who gave live births between February 2022 and December 2022. Odds ratios (ORs) for preterm birth and any congenital malformation per COVID-19 vaccination during pregnancy compared to 1:4 matched unvaccinated controls, adjusted for maternal age, residential area, employment, income, disability, month of conception, prepregnancy obesity, smoking, and severe acute respiratory syndrome coronavirus 2 infection prior to pregnancy, were calculated. We compared the risk of two outcomes between BNT162b2 and mRNA-1273. Results: Among 106,692 women who gave birth during the study period, 8,966 (8.4%) received a COVID-19 vaccination during pregnancy. Of the newborns, 7,039 (6.6%) were preterm births and 7,658 (7.2%) had congenital malformations. COVID-19 vaccination during pregnancy was associated with a comparable risk of preterm birth (OR, 1.03; 95% confidence interval [CI], 0.77–1.36) and a similar risk of congenital malformations (0.90; 95% CI, 0.72–1.12) compared to non-vaccinees. The ORs of preterm birth (1.02; 95% CI, 0.77–1.36) and congenital malformation (0.91; 95% CI, 0.73–1.14) for mRNA-1273 were comparable to those for BNT162b2. Conclusion COVID-19 vaccines during pregnancy poses no increased risk of preterm birth and congenital malformations compared to those not exposed to the vaccine, with similar risk levels observed between the two mRNA vaccines. This finding provides additional evidence supporting the safety of COVID-19 vaccines.

Background: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.