Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive or anticancer agents.Surgical intervention is generally recommended for advanced stages, but some patients may be ineligible for surgery due to systemic conditions or anatomical limitations. We present two patients who had been treated for osteoporosis with bisphosphonates and were diagnosed with stage 2 MRONJ. Their chief complaints included refractory pain, purulent discharge, and exposed bone following tooth extraction. Despite conservative treatment, the MRONJ worsened, prompting the initiation of teriparatide therapy. After teriparatide administration, the patients experienced symptom improvement, spontaneous sequestrum removal, and significant bone regeneration of vertical osteolysis. Teriparatide, a bone anabolic agent, is typically recommended as adjuvant therapy alongside surgical treatment for MRONJ. This case report illustrates the effectiveness of teriparatide monotherapy in the absence of surgical intervention, particularly for patients who cannot discontinue antiresorptive agents due to low bone mineral density.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Purpose: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methods: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). Results: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Conclusion Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson's trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

BACKGROUND: This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy. METHODS: F. nucleatum DNA was quantitatively measured in a total of 593 CRC tissues retrospectively collected from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative. RESULTS: No significant differences in survival were observed between the F.nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses according to tumor location demonstrated that disease-free survival was significantly better in F.nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal, ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariate analysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoid colon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore, the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not in a MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor location and MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treated with adjuvant chemotherapy. CONCLUSIONS: Intratumoral F. nucleatum load is a potential prognostic factor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treated with oxaliplatin-based adjuvant chemotherapy.
Chemotherapy, Adjuvant ; Colon, Descending ; Colonic Neoplasms ; Colorectal Neoplasms ; Disease-Free Survival ; DNA ; Fusobacterium nucleatum ; Fusobacterium ; Gastrointestinal Microbiome ; Humans ; Microsatellite Instability ; Microsatellite Repeats ; Multivariate Analysis ; Prognosis ; Retrospective Studies

BACKGROUND: Tumor microenvironment has recently drawn attention in that it is related with tumor prognosis. Cancer-associated fibroblast also plays a critical role in cancer invasiveness and progression in colorectal cancers. Periostin (POSTN), originally identified to be expressed in osteoblasts and osteoblast-derived cells, is expressed in cancer-associated fibroblasts in several tissue types of cancer. Recent studies suggest an association between stromal overexpression of POSTN and poor prognosis of cancer patients. METHODS: We analyzed colorectal cancer cases for their expression status of POSTN in tumor stroma using immunohistochemistry and correlated the expression status with clinicopathological and molecular features. RESULTS: High level of POSTN expression in tumor stroma was closely associated with tumor location in proximal colon, infiltrative growth pattern, undifferentiated histology, tumor budding, luminal necrosis, and higher TNM stage. High expression status of POSTN in tumor stroma was found to be an independent prognostic parameter implicating poor 5-year cancer-specific survival and 5-year progression-free survival. CONCLUSIONS: Our findings suggest that POSTN overexpression in tumor stroma of colorectal cancers could be a possible candidate marker for predicting poor prognosis in patients with colorectal cancers.
Colon ; Colorectal Neoplasms* ; Disease-Free Survival ; Fibroblasts ; Humans ; Immunohistochemistry ; Necrosis ; Osteoblasts ; Phenobarbital ; Prognosis ; Tumor Microenvironment

PURPOSE: Computational flow dynamic (CFD) study has not been widely applied in intracranial artery stenosis due to requirement of high resolution in identifying the small intracranial artery. We described a process in CFD study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. MATERIALS AND METHODS: Reconstructed 3D angiography in STL format was transferred to Magics (Materialise NV, Leuven, Belgium) for smoothing of vessel surface and trimming of branch vessels and to HyperMesh (Altair Engineering Inc., Auckland, New Zealand) for generating tetra volume mesh from triangular surface-meshed 3D angiogram. Computational analysis of blood flow in the blood vessels was performed using the commercial finite element software ADINA Ver 8.5 (ADINA R & D, Inc., Lebanon, MA). The distribution of wall shear stress (WSS), peak velocity and pressure in a patient was analyzed before and after intracranial stenting. RESULTS: Computer simulation of wall shear stress, flow velocity and wall pressure before and after stenting could be demonstrated three dimensionally by video mode according to flow vs. time dimension. Such flow model was well correlated with angiographic finding related to maximum degree of stenosis. Change of WSS, peak velocity and pressure at the severe stenosis was demonstrated before and after stenting. There was no WSS after stenting in case without residual stenosis. CONCLUSION: Our study revealed that CFD analysis before and after intracranial stenting was feasible despite of limited vessel wall dimension and could reveal change of WSS as well as flow velocity and wall pressure.
Angiography ; Arteries ; Atherosclerosis ; Blood Vessels ; Cerebral Arteries ; Characidae ; Computer Simulation ; Constriction, Pathologic ; Glycosaminoglycans ; Humans ; Lebanon ; Magic ; Stents

PURPOSE: The aim of this study was to compare the short and long-term outcomes following carotid endarterectomy (CEA) with either primary closure (PC) or patch angioplasty (PAT) performed by single center vascular surgeons. METHODS: Between November 1994 and March 2008, a total of 366 patients underwent 401 consecutive primary CEA procedures at our institution. We retrospectively reviewed patients' medical records. Two vascular surgeons prefer routine PC and one vascular surgeon prefer routine patch closure using bovine pericardial patch. Postoperative neurologic complications were determined by clinical neurologists. Restenosis was defined as >50% stenosis on follow-up duplex scan. Data was analyzed to compare the early (< or =30 days) and late results of CEA between PC group and PAT group. RESULTS: The mean follow-up duration was significantly longer in the PC group than that in the PAT group (61.7 months vs. 41.2 months, P<0.001). Coronary artery disease and combined CEA with coronary artery bypass were more common in the PAT group (39% vs. 55%, P<0.002; 4% vs. 12%, P<0.004). Perioperative ipsilateral TIA/stroke rates in the PC and PAT groups were 1.5% and 0.7% (PC=4/270 vs. PAT=1/131, P=0.564). Regarding late outcomes, Kaplan-Meier analysis failed to show any difference between 2 groups on freedom from ipsilateral transient ischemic attack (TIA)/stroke, freedom from restenosis and TIA/stroke-free survival (P=0.851, P=0.232, P=0.103, log-rank test). CONCLUSION: Our results suggest that PC following CEA is not necessarily inferior to PAT for experienced surgeons.
Angioplasty ; Constriction, Pathologic ; Coronary Artery Bypass ; Coronary Artery Disease ; Endarterectomy, Carotid ; Follow-Up Studies ; Freedom ; Humans ; Ischemic Attack, Transient ; Kaplan-Meier Estimate ; Medical Records ; Retrospective Studies

Background: DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types. Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.
Cervix Uteri ; DNA ; Female ; Genotype ; Humans ; Mass Screening ; Oligonucleotide Array Sequence Analysis ; Population Characteristics ; Prevalence ; Republic of Korea ; Vaccination ; Vaginal Smears