A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.

Objective: This study aims to investigate the clinical relevance of occipital hypoperfusion in patients with Parkinson’s disease (PD) with respect to clinical phenotype and the risk of dementia conversion. Methods: We enrolled 349 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET). Patients with PD were classified into three groups based on posterior cortical perfusion patterns on early-phase 18F-FP-CIT PET images: PD with preserved posterior cortical perfusion (n=186), PD with parieto-temporal hypoperfusion (n=84), and PD with parieto-temporo-occipital hypoperfusion (n=79). Baseline clinical features and dementia conversion risk were compared across PD groups. Results: Patients with preserved posterior cortical perfusion were younger than those in the other PD groups. Compared with the other groups, the parieto-temporo-occipital hypoperfusion group tended to have lower Cross-Cultural Smell Identification Test scores, a higher prevalence of rapid eye movement sleep behavior disorder, higher Unified PD Rating Scale motor scores, and more severe reductions in striatal dopamine transporter availability. The risk of dementia conversion was lower in patients with preserved posterior cortical perfusion than in those with posterior cortical hypoperfusion. However, the risk of dementia conversion did not differ between the parieto-temporal and parieto-temporo-occipital hypoperfusion groups. Conclusion Additional occipital hypoperfusion was not associated with an imminent risk of dementia conversion in patients with PD with posterior cortical hypoperfusion. Nonetheless, occipital involvement may serve as an indicator of the diffuse malignant subtype of PD.

Spinal melanocytoma (SMC) is a rare, slow-growing tumor arising from melanocytes in the spinal cord. We report a patient with a cervical intra- and extradural spinal tumor causing progressive weakness and numbness. On magnetic resonance imaging (MRI), the lesion showed intense homogeneous enhancement, similar to that seen in common neurogenic spinal tumors. After complete resection, pathological examination confirmed melanocytoma. A review of previously reported cases identified 26 reports of this tumor in the cervical spine, most of which were treated with complete surgical resection. Gross total resection is the preferred treatment, although radiation therapy may be considered when residual tumor remains. We report a 25-year-old male patient who presented with progressive weakness and numbness in both the upper and lower extremities for 3 months. MRI showed homogeneous enhancement. The mass compressed the spinal cord at C6–7 and extended through the neural foramen. Based on the MRI findings, spinal schwannoma was suspected preoperatively. Surgical resection was performed with laminectomy, durotomy, and right facetectomy. A dark-colored mass with well-demarcated margins was exposed and removed. Postoperative MRI confirmed complete removal of the mass. The patient recovered well, and his preoperative myelopathic symptoms gradually improved. SMC is a rare benign tumor that may be mistaken for schwannoma. The treatment of choice is gross total resection.

Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Background: Dual energy X-ray absorptiometry (DXA) measurements vary among instruments from different manufacturers. This study aimed to assess the correlation between bone mineral density (BMD) and body composition measured by the GE Lunar Prodigy and Hologic Horizon W DXA systems and to develop conversion equations. Methods: A total of 120 healthy volunteers (59 males, 61 females) aged 20 to 70 years were scanned on both DXA systems on the same day. BMD was measured at the lumbar spine (L1-L4) and bilateral femurs. Body composition parameters were measured for the whole body and regional sites. Bland-Altman analysis, Pearson correlation, and concordance correlation coefficient (CCC) were used to assess agreement. Linear regression was performed to derive conversion equations. Results: The Hologic system measured BMD values 14% to 20% lower at the lumbar spine and 8% to 17% lower at femoral sites compared to the GE Lunar system (all P<0.0001). Lean mass values were 4% to 10% lower on the Hologic system. Very strong correlations were observed for both BMD (r=0.944-0.980) and lean mass (r=0.963-0.984). Cross-calibration equations were developed for all measurement sites. Conclusions Despite significant systematic differences, there was very high correlation between the two DXA systems. The conversion equations can facilitate comparison of measurements between these systems in clinical practice and research.

Background: Posterior fossa group A (PFA) ependymoma is a lethal pediatric brain tumor drivenpredominantly by epigenetic dysregulation. Enhancer of Zeste Homologs Inhibitory Protein (EZHIP) is a defining oncogenic factor in PFA ependymoma that inhibits PRC2 activity, inducing a global loss of H3K27me3 and sustaining aberrant developmental transcriptional programs. Although the metabolic modulator, metformin, reduces EZHIP protein levels, the mechanisms governing EZHIP regulation remain undefined. Methods: We generated a stable HEK293T reporter cell expressing HA- and RFP-taggedEZHIP together with a GFP viability control, enabling quantitative and viability-normalized assessment of EZHIP abundance. In silico post-translational modification prediction was performed using PhosphoSitePlus and NetPhos 3.1 to identify candidate regulatory residues and upstream kinases. A focused panel of pathway targeting compounds was evaluated using fluorescence-based high-throughput screening, followed by secondary validation including cell counting, LC 50 (half-maximal lethal concentration) analysis, and Western blotting. Results: Computational analyses identified multiple high-confidence serine phosphorylationsites on EZHIP and implicated AMPK, MAPK, PKC, AKT, and CK2 signaling pathways. High-throughput screening revealed that activation of the AMPK axis robustly suppressed EZHIP protein levels.Secondary validation demonstrated that biguanides activating AMPK reduced EZHIP abundance independently of cytotoxicity and restored global H3K27me3 levels. In contrast, PKC activation increased EZHIP protein abundance. Conclusion Our study identifies EZHIP as a dynamically regulated oncoprotein controlled by post-translational signaling pathways. AMPK and PKC exert opposing effects on EZHIP stability, defining actionable regulatory mechanisms for therapeutic targeting in EZHIP-driven cancers.

Background/Aims: Both endoscopic resection (ER) and transanal surgery (TAS) are minimally invasive treatment options that allow organ preservation in early rectal tumors. We conducted a meta-analysis to compare treatment outcomes between the 2 treatments. Methods: We searched all relevant studies published until January 2024 that examined the comparative outcomes between ER and TAS for rectal tumors, including adenoma, adenocarcinoma, and neuroendocrine tumor (NET). TAS included transanal excision, transanal endoscopic microsurgery, and transanal minimally invasive surgery. Results: Seventeen studies with a total of 1,569 patients were included in this meta-analysis. For adenoma/adenocarcinoma, the R0 resection rate did not differ between ER and TAS (risk ratio [RR], 0.99; 95% confidence interval [CI], 0.94–1.03). For NET, the R0 resection rate was lower in the ER group than in the TAS group (RR, 0.76; 95% CI, 0.68–0.84) and the procedure time for ER was shorter than that for TAS. For both adenoma/adenocarcinoma and NET, ER and TAS did not differ in terms of complication rates, additional surgery, and recurrence. Conclusions ER and TAS showed similar treatment outcomes for adenoma/adenocarcinoma. Considering that TAS typically incurs higher costs than ER, ER may be favored in the treatment of rectal adenoma/adenocarcinoma. For rectal NET, TAS showed a superior R0 resection rate than ER. However, given that TAS requires a long procedure time, expensive equipment, and complex manipulations, TAS may be considered selectively for large NETs with suspected deep tumorous infiltration.

Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection commonly observed in immunocompromised patients, necessitating prompt diagnosis and treatment. This review evaluates the diagnostic performance of various tests used for PJP diagnosis through a comprehensive literature review. Additionally, we propose a diagnostic algorithm tailored to non-human immunodeficiency virus immunocompromised patients, considering the specific characteristics of current medical resources in Korea.