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.

Background: Transient receptor potential canonical (TRPC) channels are non-selective cationic channels with perme‑ ability to ­Ca2+ and ­Na+ . Despite their importance, there are currently few studies on TRPC in the periodontal ligament (PDL) and bone cells in the dental field. To provide biological information regarding TRPC in PDL cells and periodontal tissue, we evaluated TRPC channels expression in the osteoblast differentiation of PDL cells and periodontitis-induced tissue. Human PDL cells were cultured in osteogenic differentiation media for 28 days, and the expression of Runx2, osteocalcin (OCN), and TRPC1, 3, 4, and 6 was evaluated by real-time PCR. In ligature-induced periodontitis mice, the alveolar bone and osteoid areas, the osteoclast number, and the expression of Runx2, OCN, TRPC3, and TRPC6 was evaluated by H&E staining, TRAP staining, and immunohistochemistry, respectively. Results: In the PDL cell differentiation group, TRPC6 expression peaked on day 7 and TRPC3 expression generally increased during differentiation. During the 28 days of periodontitis progression, alveolar bone loss and osteoclast numbers increased compared to the control group during the experimental period and the osteoid area increased from day 14. TRPC6 expression in the periodontitis group increased in the PDL area and in the osteoblasts compared to the control group, whereas TRPC3 expression increased only in the PDL area on days 7 and 28. Conclusions These results indicate changes of TRPC3 and TRPC6 expression in PDL cells that were differentiating into osteoblasts and in periodontitis-induced tissue, suggesting the need for research on the role of TRPC in osteo‑ blast differentiation or periodontitis progression.

Increases of neutrophils and osteoclasts are pathological changes of periodontitis. RANKL is an osteoclast differentiation factor. The effect of periodontopathogen LPS on RANKL-expressing neutrophils has not been clarified yet. We evaluated numerical changes of RANKL-expressing neutrophils in air pouches of mice injected with LPSs of Fusobacterium nucleatum and Porphyromonas gingivalis. Mice with air pouches were assigned into saline (C)-, E. coli LPS- (Ec LPS)-, F. nucleatum LPS (Fn LPS)-, P. gingivalis LPS (Pg LPS)-, and Fn LPS and Pg LPS (Fn + Pg LPS)-injected groups. CD11b +Ly6G + neutrophils and CD11b +Ly6G+RANKL + neutrophils in blood and air pouch exudates were determined by flow cytometry. In blood, compared to the C group, the Fn LPS group showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils whereas the Pg LPS group showed no significant differences. These increases in the Fn LPS group were not different to those in the Ec LPS group. In exudates, Fn LPS and Pg LPS groups showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils compared to the C group. Increased levels in the Fn LPS group were not different to those in the Ec LPS group, but Pg LPS group was lower than those in the Ec LPS group. In blood and exudates, the Fn+ Pg LPS group showed no difference in levels of these neutrophils compared to the Ec LPS group. LPSs of F. nucleatum and P. gingivalis increased RANKL-expressing neutrophils although the degrees of increases were different. These suggest that periodontopathogen LPS can act as a stimulant to increase RANKL-expressing neutrophils.

Increases of neutrophils and osteoclasts are pathological changes of periodontitis. RANKL is an osteoclast differentiation factor. The effect of periodontopathogen LPS on RANKL-expressing neutrophils has not been clarified yet. We evaluated numerical changes of RANKL-expressing neutrophils in air pouches of mice injected with LPSs of Fusobacterium nucleatum and Porphyromonas gingivalis. Mice with air pouches were assigned into saline (C)-, E. coli LPS- (Ec LPS)-, F. nucleatum LPS (Fn LPS)-, P. gingivalis LPS (Pg LPS)-, and Fn LPS and Pg LPS (Fn + Pg LPS)-injected groups. CD11b +Ly6G + neutrophils and CD11b +Ly6G+RANKL + neutrophils in blood and air pouch exudates were determined by flow cytometry. In blood, compared to the C group, the Fn LPS group showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils whereas the Pg LPS group showed no significant differences. These increases in the Fn LPS group were not different to those in the Ec LPS group. In exudates, Fn LPS and Pg LPS groups showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils compared to the C group. Increased levels in the Fn LPS group were not different to those in the Ec LPS group, but Pg LPS group was lower than those in the Ec LPS group. In blood and exudates, the Fn+ Pg LPS group showed no difference in levels of these neutrophils compared to the Ec LPS group. LPSs of F. nucleatum and P. gingivalis increased RANKL-expressing neutrophils although the degrees of increases were different. These suggest that periodontopathogen LPS can act as a stimulant to increase RANKL-expressing neutrophils.

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.

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

OBJECTIVES: Type 2 diabetes, a leading cause of cardiovascular disease, is well known for its association with accelerated atherosclerosis. Adiponectin and tumor necrosis factor - alpha (TNF-alpha), which are produced and secreted in adipose tissue, have been suggested as predictors for cardiovascular disease. However, little is known about the influence of adiponectin and TNF-alpha ratio on the progression of carotid atherosclerosis in newly diagnosed type 2 diabetic patients. This study was conducted to evaluate the influence of serum adiponectin/TNF-alpha levels on the progression of carotid atherosclerosis. METHODS: One hundred eleven newly diagnosed type 2 diabetes patients were enrolled. Anthropometric and biochemical data including serum adiponectin, TNF-alpha were measured for each participant. Also we measured carotid intima-media thickness (CIMT) at baseline and at 1 year follow-up (n=81). We finally examined the relationship among serum adiponectin over TNF-alpha levels (ADPN/TNF-alpha), baseline CIMT, and progression of CIMT at 1 year. RESULTS: ADPN/TNF-alpha negatively correlated with baseline CIMT (r=-0.231, p=0.025). Moreover, progression of CIMT was significant at 1 year (0.011+/-0.138 mm). There was a negative correlation between ADPN/TNF-alpha and progression of CIMT at 1 year (r=-0.172, p=0.038). In multiple regression analysis, age and HbA1c were found to be independent risk factors for baseline CIMT. However, only HbA1c was an independent risk factor for the progression of CIMT. CONCLUSION: ADPN/TNF-alpha was negatively associated with baseline CIMT and the progression of CIMT at 1 year. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.
Adiponectin* ; Adipose Tissue ; Atherosclerosis ; Cardiovascular Diseases ; Carotid Artery Diseases ; Carotid Intima-Media Thickness* ; Diabetes Mellitus ; Follow-Up Studies ; Humans ; Risk Factors ; Tumor Necrosis Factor-alpha*