Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Objective: Written exposure therapy (WET) is exposure therapy for post-traumatic stress disorder (PTSD). Compared to evidencebased treatments for PTSD, WET requires only five sessions, has a shorter session time, and no between-session assignments. The current study examined the efficacy of WET among Korean patients with PTSD due to various traumatic events on PTSD symptoms, depressive symptoms, and global functioning levels. Methods: The study recruited 41 patients with a current primary diagnosis of PTSD in psychiatric outpatient clinics. Assessments were conducted at baseline, and at 6, 12, and 24 weeks following the first treatment session. Results: In total, 25 patients started WET. Findings showed a significant reduction in the rate of PTSD diagnosis and symptom severity scores. Fourteen of 23 (60.9%) patients at 6 weeks, 15 of 22 (68.2%) patients at 12 weeks, and 14 of 18 (77.8%) patients at 24 weeks no longer met the diagnosis of PTSD. Depressive symptoms and global function scores also improved after WET. The dropout rate was 8% (n=2). Conclusion This study suggests the feasibility of implementing WET among various types of patients with PTSD in Korea and other Asian countries.

Objective: Written exposure therapy (WET) is exposure therapy for post-traumatic stress disorder (PTSD). Compared to evidencebased treatments for PTSD, WET requires only five sessions, has a shorter session time, and no between-session assignments. The current study examined the efficacy of WET among Korean patients with PTSD due to various traumatic events on PTSD symptoms, depressive symptoms, and global functioning levels. Methods: The study recruited 41 patients with a current primary diagnosis of PTSD in psychiatric outpatient clinics. Assessments were conducted at baseline, and at 6, 12, and 24 weeks following the first treatment session. Results: In total, 25 patients started WET. Findings showed a significant reduction in the rate of PTSD diagnosis and symptom severity scores. Fourteen of 23 (60.9%) patients at 6 weeks, 15 of 22 (68.2%) patients at 12 weeks, and 14 of 18 (77.8%) patients at 24 weeks no longer met the diagnosis of PTSD. Depressive symptoms and global function scores also improved after WET. The dropout rate was 8% (n=2). Conclusion This study suggests the feasibility of implementing WET among various types of patients with PTSD in Korea and other Asian countries.

Periodontitis is a bacteria-induced inflammatory disease associated with alveolar bone loss. Osteoclast is a macrophage-lineage cell that exhibits phagocytic activity; however, osteoclast phagocytic activity has not been demonstrated under pathological conditions. Diabetes is a pathological condition that exacerbates alveolar bone loss via periodontitis; therefore, we examined phagocytic osteoclasts in diabetic rats that had periodontitis. The rats were divided into the control (C), periodontitis (P), and diabetes with periodontitis (DP) groups. Diabetes and periodontitis were induced by streptozotocin injection and ligature of the mandibular first molars, respectively. On days 3 and 20 after the ligature, the rats were sacrificed, and osteoclasts containing inclusions were quantified by tartrate-resistant acid phosphatase staining. On day 3, there were more osteoclasts containing inclusions in the DP group than in the C group. Among inclusions, osteocyte-like cells and dense bodies were more frequently observed in the DP group than in the C group. Cytoplasm-like structures were elevated more in the DP group than in the C and P groups. However, no differences were observed on day 20. Interestingly, some osteoclasts were in contact with the osteocytes within the exposed lacunae and contained several inclusions within a large vacuole. Thus, the elevation of phagocytic osteoclasts in rats with diabetes and periodontitis provides insight into the role of osteoclast phagocytic activity under pathological conditions.

Cognitive deficits due to posttraumatic stress disorder (PTSD) affect patients’ social and occupational functioning and lead to social costs. Thus, it is important to understand the nature and extent of PTSD-related neurocognitive deficits to clarify the mechanisms underlying cognitive changes, identify factors that interfere with treatment, and help interpret clinical profiles. This study reviewed recent studies on the relationships between PTSD and neurocognitive domains. The magnitude of the influence of PTSD differs across cognitive function domains. Also, the extent of the effect on any given domain may also differ according to the type of trauma experienced by the subject. In addition to its negative effects on cognitive functioning, PTSD was associated with increased response to threats or trauma-related stimuli, which compromised task performance. Although each PTSD symptom may have a different effect on each cognitive function, it was difficult to generalize the results. This study is significant in that our conclusions, which emerged through a review of studies regarding the relationship between PTSD and cognitive functioning, provide a theoretical basis for further research.

BACKGROUND AND PURPOSE: Visual assessment of medial temporal-lobe atrophy (MTA) has been quick, reliable, and easy to apply in routine clinical practice. However, one of the limitations in visual assessments of MTA is the lack of widely accepted age-adjusted norms and cutoff scores for MTA for a diagnosis of Alzheimer's disease (AD). This study aimed to determine the optimal cutoff score on a T1-weighted axial MTA Visual Rating Scale (VRS) for differentiating patients with AD from cognitively normal elderly people. METHODS: The 3,430 recruited subjects comprising 1,427 with no cognitive impairment (NC) and 2003 AD patients were divided into age ranges of 50–59, 60–69, 70–79, and 80–89 years. Of these, 446 participants (218 in the NC group and 228 in the AD group) were chosen by random sampling for inclusion in this study. Each decade age group included 57 individuals, with the exception of 47 subjects being included in the 80- to 89-year NC group. The scores on the T1-weighted axial MTA VRS were graded by two neurologists. The cutoff values were evaluated from the area under the receiver operating characteristic curve. RESULTS: The optimal axial MTA VRS cutoff score from discriminating AD from NC increased with age: it was ≥as ≥1, ≥2, and ≥3 in subjects aged 50–59, 60–69, 70–79, and 80–89 years, respectively (all p < 0.001). CONCLUSIONS: These results show that the optimal cutoff score on the axial MTA VRS for diagnosing of AD differed according to the decade age group. This information could be of practical usefulness in the clinical setting.
Aged ; Alzheimer Disease* ; Atrophy* ; Cognition Disorders ; Dementia* ; Diagnosis ; Humans ; Korea* ; Pemetrexed ; ROC Curve

We have previously reported a novel synthetic compound KMS99220 that prevented degeneration of the nigral dopaminergic neurons and the associated motor deficits, suggesting a neuroprotective therapeutic utility for Parkinson's disease. Microglia are closely associated with neuroinflammation, which plays a key role in the pathogenesis of neurodegenerative diseases. In this study, we investigated the effects of KMS99220 on the signaling involving AMP-activated protein kinase (AMPK) and heme oxygenase-1 (HO-1), the enzymes thought to regulate inflammation. KMS99220 was shown to elevate the enzyme activity of purified AMPK, and phosphorylation of cellular AMPK in BV2 microglia. It increased the level of HO-1, and this was attenuated by AMPK inhibitors. KMS99220 lowered phosphorylation of IκB, nuclear translocation of NFκB, induction of inducible nitric oxide synthase, and generation of nitric oxide in BV2 cells that had been challenged with lipopolysaccharide. This anti-inflammatory response involved HO-1, because both its pharmacological inhibition and knockdown of its expression abolished the response. The AMPK inhibitors also reversed the anti-inflammatory effects of KMS99220. The induction of HO-1 by KMS99220 occurred within 1 h, and this appeared not to involve the transcription factor Nrf2, because Nrf2 knockdown did not affect the compound's HO-1 inducing- and anti-inflammatory effects in this time window. These findings indicated that KMS99220 leads to AMPK-induced HO-1 expression in microglia, which in turn plays an important role in early anti-inflammatory signaling. Together with its neuroprotective property, KMS99220 may serve as a feasible therapeutic agent against neuroinflammation and neurodegeneration.
AMP-Activated Protein Kinases* ; Dopaminergic Neurons ; Heme Oxygenase-1 ; Inflammation ; Microglia ; Neurodegenerative Diseases ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Parkinson Disease ; Phosphorylation ; Transcription Factors

To determine the effect of the tumor necrosis factor-α (TNF-α) in odontoclast formation, we administrated a TNF-α inhibitor in rats with diabetes rats with periodontitis. The rats included in the study were divided into three groups: control rats without diabetes or periodontitis (the C group), rats with periodontitis and diabetes (the PD group), and rats with periodontitis and diabetes treated by infliximab, the TNF inhibitor (the PD+infliximab group). The PD and PD+ infliximab groups received intravenous administrations of streptozotocin (STZ, 50 mg/kg) to induce diabetes. After 7 days of STZ injections, the mandibular first molars were ligatured to induce periodontitis. The PD+infliximab group was intrapenitoneally administrated by infliximab (5 mg/kg). On days 3 and 20 after the ligature administration, odontoclast formation along root surfaces was evaluated by tartrate resistant acid phosphatase (TRAP) staining and cathepsin K immunohistochemistry. On day 3, the number of TRAP- and cathepsin K-positive cells increased more so in the PD group than in the C group. The PD+infliximab group showed a lower number of positive cells than the PD group. There was no difference in all the groups on day 20. On day 3, the cathepsin-K positive multinucleated and mononucleated cells were higher in the PD group than in the C group. The number of cathepsin-K positive multinucleated cells was lower in the PD+infliximab group than in the PD group. The PD group showed more cathepsin K-positive cells in the furcation and distal surfaces than the c group. The Cathepsin K-positive cells of the PD+infliximab group were lower than that of the PD group in furcation. These results suggest that TNF-α stimulates odontoclast formation in diabetes with periodontitis.
Acid Phosphatase ; Administration, Intravenous ; Animals ; Cathepsin K ; Cathepsins ; Immunohistochemistry ; Infliximab ; Ligation ; Molar ; Necrosis ; Osteoclasts* ; Periodontitis* ; Rats* ; Streptozocin

PURPOSE: To study the safety and efficacy of corneal reshaping and small-aperture inlays and compare the clinical results. METHODS: From February 2014 to November 2014, 22 corneal reshaping inlays were inserted at Asan Medical Center and from October 2012 to March 2013, 26 small-aperture inlay surgeries were performed: 6 eyes at Asan Medical Center and 20 eyes at Samsung Medical Center. The preoperative and postoperative parameters were reviewed retrospectively and included monocular uncorrected distance visual acuity (UDVA; log MAR), uncorrected near visual acuity (UNVA; log MAR), refraction and corneal curvature based on automated refractor keratometry, reading distance and patient satisfaction. RESULTS: In the hydrogel inlay group, preoperative mean monocular UNVA was 0.83 +/- 0.05 and monocular UDVA 0.07 +/- 0.03. At 6 months, mean monocular UNVA was 0.23 +/- 0.05 and UDVA 0.05 +/- 0.02. The most preferred mean reading distance in the hydrogel inlay group was 39.38 +/- 3.18 cm. In the small-aperture inlay group, preoperative mean monocular UNVA was 0.4 +/- 0.06 and monocular uncorrected visual acuity 0.27 +/- 0.04. At 6 months, mean monocular UNVA was 0.11 +/- 0.02 and UDVA 0.09 +/- 0.05 and the most preferred mean reading distance was 44.23 +/- 5.17 cm. Although 85% of patients in the corneal reshaping inlay group were satisfied or very satisfied, only 20% of patients in the small-aperture inlay group were satisfied. CONCLUSIONS: Both inlays are considered good options for correcting presbyopia. However, postoperative satisfaction score was higher and less glare symptoms were reported in the hydrogel inlay group.
Chungcheongnam-do ; Follow-Up Studies* ; Glare ; Humans ; Hydrogel* ; Inlays* ; Patient Satisfaction ; Presbyopia* ; Retrospective Studies ; Visual Acuity

Vulvar hematomas are uncommon outside of the obstetric population and may be the result of trauma to the perineum. Vulvar hematomas most often present with low abdominal pain and urologic and neurologic symptoms. The vulva has rich vascularization that is supplied by the pudendal artery, a branch of the anterior division of the internal iliac artery. We describe a rare case of a 15-cm-sized vulvar hematoma with the suggested rupture of a pseudoaneurysm of the left pudendal artery without trauma injury. A 14-year-old girl presented with sudden pain and swelling in her left labium and was successfully treated with selective arterial embolization and surgical evacuation. We provide a literature review and discuss patient treatment and management strategies.
Abdominal Pain ; Adolescent ; Aneurysm, False* ; Arteries* ; Female ; Hematoma* ; Humans ; Iliac Artery ; Neurologic Manifestations ; Perineum ; Rupture* ; Vulva