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Background Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs). Methods Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab. Results For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone. Conclusions The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN. Clinical Trial Registration NCT01527877.

In this study, the delivery quality assurance (DQA) results of commercially available dosimetric systems (ionization chamber and EBT film, MapCHECK, ArcCHECK, and dosimetry check (DC) software) for helical tomotherapy (HT) were compared, and the feasibility of performing pretreatment using MapCHECK, ArcCHECK, and DC for HT, instead of ionization chambers and EBT films, was assessed. Sixty-five HT-treated patients were considered. Point dose differences, dose profiles, and gamma passing rates were used to evaluate the agreement between the calculated and the measured data, and the outcomes of the four DQA devices were compared in various clinical cases. The calculated and the measured point doses were within ±5% of each other. In terms of the root-mean-square error (RMSE), the point dose differences were within 2.9 for the four tested devices in all of the studied cases. Gamma analysis was performed based on the 3%/3 mm and 2%/2 mm passing rate criteria. In terms of the average RMSE, the gamma passing rates of the four tested DQA devices were within 2.85 (3%/3 mm) and 7.30 (2%/2 mm). These DQA systems could be used interchangeably for routine DQA pretreatment in HT cases.

Background: Modern total ankle arthroplasty (TAA) prostheses are uncemented press-fit designs whose stability is dependent on bone ingrowth. Preoperative insufficient bone density reduces initial local stability at the bone-implant interface, and we hypothesized that this may play a role in periprosthetic osteolysis. We aimed to investigate the preoperative bone density of the distal tibia and talus and compare these in patients with and without osteolysis. Methods: We enrolled 209 patients (218 ankles) who underwent primary TAA using the HINTEGRA prosthesis. The overall mean follow-up duration was 66 (range, 24-161) months. The patients were allocated into 2 groups according to the presence of periprosthetic osteolysis: the osteolysis group (64 patients, 65 ankles) and nonosteolysis group (145 patients, 153 ankles). Between the 2 groups, we investigated and compared the radiographic outcomes, including the Hounsfield unit (HU) value around the ankle joint and the coronal plane alignment. Results: HU values of the tibia and talus measured at 5 mm from the reference points were higher than those at 10 mm in each group. However, comparing the osteolysis and nonosteolysis groups, we found no significant intergroup difference in HU value at every measured level in the tibia and talus ( P > .05). Concerning the coronal plane alignment, there were no significant between-group differences in the tibiotalar and talar tilt angles ( P > .05). Conclusion: Patients with osteolysis showed similar preoperative bone density of the distal tibia and talus compared with patients without osteolysis. Our results suggest that low bone density around the ankle joint may not be associated with increased development of osteolysis. Level of Evidence: Level III, retrospective cohort study.

IntroductionProsthesis of antibiotic-loaded acrylic cement (PROSTALAC) is widely used in two-stage revision arthroplasty in periprosthetic joint infection (PJI) after total hip arthroplasty (THA). In our institution, we encountered several cases of acetabular cement spacer dislodgement. The aim of this study was to compare the results of two-stage revision arthroplasties with antibiotic-loaded cement spacers with or without screws on the acetabulum for PJI.Patients and methodsThis retrospective study included 44 patients who underwent a two-stage revision THA for PJI from June 2007 to May 2017. We divided the patients into two groups: group 1 consisted of 21 patients (21 hips) who underwent two-stage revision arthroplasty with screw augmentation, while group 2 consisted of 23 patients (23 hips) who underwent the same surgery without screw augmentation at the acetabular cement spacer. We compared the migration and dislodgement of the acetabular cement spacer between the two groups.ResultsBefore the second-stage surgery, there was less vertical migration of the cement spacer in group 1 compared to group 2 (1.2 mm vs 3.1 mm,p< 0.001). There was also less medial migration of the cement spacer in group 1 (0.6 mm vs 1.6 mm,p= 0.001). After the first stage, the mean Harris Hip score was significantly higher in group 1 than in group 2 (75 vs 65,p= 0.033). Cement spacer rotation or total movement out of the acetabular area occurred in six patients, all in group 2. After first stage reinfection occurred in two patients, one in each group.ConclusionsScrew augmentation to the acetabulum in the first-stage surgery provides better stability of acetabular antibiotic cement spacers without increasing reinfection rate.

BACKGROUND Gastric ‘indefinite for neoplasm/dysplasia’ (IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management. AIM To determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions. METHODS In total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection (n = 134), surgery (n = 22), and follow-up endoscopic biopsy (n = 305) were performed to confirm the diagnosis. The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia (60%) or atypical epithelia (40%) at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases. RESULTS Four clinical factors [age ≥ 60 years (2.445, 95%CI: 1.305-4.580, P = 0.005), endoscopic size ≥ 10 mm (3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion (5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding (4.056, 95%CI: 1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium (25.575, 95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI: 1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were 91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change (5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review. CONCLUSION More than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.

To determine whether microfracture with bone marrow aspirate concentrate (BMAC) improves functional outcome and cartilage regeneration better than microfracture alone in patients undergoing high tibial osteotomy (HTO) for medial unicompartmental osteoarthritis (OA). Among 436 patients treated with HTO for medial unicompartmental OA with varus deformity between 2010 and 2016, clinical outcomes were retrospectively compared between the microfracture alone group (group I, 43 cases) and microfracture with BMAC augmentation group (group II, 48 cases). Of these, 64 patients underwent a second-look arthroscopic assessment. Clinical outcomes were compared based on the Knee Society Score (KSS), International Knee Documentation Committee (IKDC) subjective score, and Western Ontario and McMaster Universities Arthritis Index (WOMAC). Cartilage regeneration was assessed according to Koshino’s staging system and the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. At the last follow-up, there were no significant intergroup differences in terms of KSS for pain and function (p > 0.05). Moreover, WOMAC scores were similar between the two groups (p > 0.05). Regarding second-look arthroscopy findings, according to Koshino’s staging system, there was no significant intergroup difference in terms of defect coverage (p = 0.187). However, group II showed a significantly better mean CRA score than group I (p = 0.035). There were no significant differences in clinical outcomes and cartilage regeneration between the groups. However, the CRA score was significantly higher with BMAC augmentation and microfracture than microfracture alone. Therefore, BMAC augmentation had a synergistic effect for a better cartilage regeneration, although studies with a longer follow-up might help to confirm whether microfracture with BMAC augmentation would ensure better clinical outcomes than microfracture alone for the treatment of knee OA.

Background The oropharyngeal cancer (OPC) constitutes a distinct clinical subset of head and neck squamous cell carcinoma with high prevalence of HPV-associated tumorigenesis. However, the relationship between tumor molecular types and immune microenvironment has not been systematically delineated in OPCs. In this study, we classified the OPCs into three different molecular subtypes regarding their immunological character by comprehensive molecular profiling by RNA-seq and multiplexed immunohistochemistry (IHC). Methods The 37 surgically resected primary OPC tumors were analyzed, and the HPV status was evaluated by p16 IHC. The transcriptome profiling of tumors by RNA-seq classified OPCs into three molecular subtypes based on t-SNE plotting. The immune microenvironment of each subtype was investigated using VECTRA spectral imaging system in terms of CD8 T cell and macrophage infiltration patterns, as well as T cell exhaustion maker expressions. The 10 OPC patients treated with anti-PD-1/PD-L1 blockade were also classified into three subtypes and their therapy response was compared. Results We divided OPCs into Immune-rich (IR), mesenchymal (MS), and classical (CL) subtypes by RNA-seq clustering analysis. All IR type tumors were HPV-positive, whereas most CL types (7 out of 8) were HPV-negative. MS type showed mixed HPV status (HPV-positive in 5/14). The IR type showed favorable prognosis compared with poor prognosis of CL type, and MS type showed intermediate survival outcome. The IR type tumors showed high enrichment of adaptive immune response, T cell exhaustion, and cell cycle gene signature implying their highly immunogenic properties. The multiplexed IHC confirmed plenty of PD-1+CD8 T cells and type I macrophages infiltrating tumor nest in IR types. The MS type was characterized by upregulation of muscle, extracellular matrix, and TGF-β signatures with scant CD8 T cell signature expression. The IHC analysis of MS type showed exclusion of CD8 T cells from tumor nest that might be related to their high TGF-β-response signature (TBRS) score. CL types were related to high xenobiotic catabolism signatures, and showed low level of CD8 T cell infiltrations with focal CD73 expression. Among 10 OPC patients with anti-PD-1/PD-L1 blockade treatment, the IR type patients showed durable therapy response (3 of 4 patients), whereas CL type patients showed early progression on the treatment (3 of 4 patients). Conclusions Our comprehensive analysis reveals that OPCs can be classified into three distinct subtypes based on their immune microenvironment properties. The three molecular subtypes showed distinct therapy response on anti-PD-1/PD-L1 blockade. These findings are pertinent to develop predictive markers on immunotherapy and to design combination immunotherapy strategies in OPC patients. Citation Format: Min Hwan Kim, Jae-Hwan Kim, Dong Min Jung, Jae Woo Choi, Soo Jin Heo, Kyoung-Ho Pyo, Min Hee Hong, Byoung Chul Cho, Hye Ryun Kim. Comprehensive molecular profiling reveals distinct immunemicroenvironment subtypes of oropharyngeal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4946.

Reportedly policosanols (PCs) have various beneficial functionalities on health. A gas chromatography-tandem mass spectrometry (GC-MS/MS) with a low limit of detection (LOD), and high specificity, recovery, and precision was successfully established for the PC analysis in vegetable oils. The LODs for the PCs were in the range of 0.002 to 0.016 μg/mL. The relative standard deviation (RSD) for the repeated analysis of PCs was less than 3.356%. The mean recoveries for spiked heptacosanol and octacosanol in vegetable oil were 102.3% and 106.3%, respectively. The total PC contents in the vegetable oils varied from 3.01 to 427.83 mg/kg oil. Perilla seed, grape seed, and rice bran oils were found to be highly rich sources of PCs, containing 427.83, 245.15, and 171.17 mg PCs/kg oil, respectively. Corn, sesame, and soybean oils contained only a negligible quantity of PCs. The PC composition in vegetable oils was greatly source dependent. In perilla seed oil, octacosanol was the single most predominant component, representing 55.93% of the total PC. In grape seed oil, however, hexacosanol is the most abundant PC, followed by octacosanol, tetracosanol, and triacontanol in a decreasing order. The major PCs in rice bran oil were triacontanol, octacosanol, hexacosanol, and tetracosanol, which constituted over 87.3% of the total PC. This represents the 1st report on the composition and contents of PC in most vegetable oils analyzed here. Practical Application: The information might be used for the development of vegetable oil products with beneficial functionality.

Effects of catechins and green tea extract (GTE) on the photosensitized singlet oxygen oxidation of linoleic acid were studied. Epigallocatechin gallate (EGCG) showed the highest antioxidant activity, followed by gallocatechin gallate, epigallocatechin, and epicatechin in a decreasing order. α-Tocopherol showed strong antioxidative activity at the initial oxidation stage, but its antioxidative property rapidly decreased with illumination time. EGCG showed significantly stronger antioxidative activity than α-tocopherol at the later oxidation stage (p

A 51-year-old highly fit man presented for dyspnea with strenuous aerobic exercise. The patient was asymptomatic and all tests were normal at rest. With increasing exercise intensity, he suddenly complained of dyspnea and showed a severe exercise-induced hypoxemia with an excessive alveolar-arterial oxygen tension difference. In agitated saline contrast echocardiography at peak exercise, a large amount of left to right shunt was identified after > 5 cardiac cycles, which suggests the presence of exercise-induced intrapulmonary arteriovenous shunt in this patient.

The chemical properties and oxidative stability of perilla oils obtained from roasted perilla seeds as affected by extraction methods (supercritical carbon dioxide [SC-CO(2)], mechanical press, and solvent extraction) were studied. The SC-CO(2) extraction at 420 bar and 50 °C and hexane extraction showed significantly higher oil yield than mechanical press extraction (P < 0.05). The fatty acid compositions in the oils were virtually identical regardless of the extraction methods. The contents of tocopherol, sterol, policosanol, and phosphorus in the perilla oils greatly varied with the extraction methods. The SC-CO(2) -extracted perilla oils contained significantly higher contents of tocopherols, sterols, and policosanols than the mechanical press-extracted and hexane-extracted oils (P < 0.05). The SC-CO(2) -extracted oil showed the greatly lower oxidative stability than press-extracted and hexane-extracted oils during the storage in the oven under dark at 60 °C. However, the photooxidative stabilities of the oils were not considerably different with extraction methods.

Purpose To determine the diagnostic performance of bedside assessment of end-tidal alveolar dead space fraction (ADSF) for pulmonary embolism (PE) and whether the use of additional ADSF assessment following D-dimer assay can improve the diagnostic accuracy in suspected PE patients in the emergency department. Methods A prospective observational study of 112 consecutive adult patients suspected of PE of whom 102 were eligible for analysis. ADSF was calculated using arterial carbon dioxide and end-tidal carbon dioxide. An ADSF less than 0.2 was considered normal. Results PE was confirmed in 11 (10.8%) of 102 patients. D-dimer assay alone as a reference standard test for PE had a sensitivity of 100%, specificity of 38.5% and false negativity of 0%. Area under the receiver-operator characteristic curve for the diagnosis of PE using ADSF values alone was 0.894, Sensitivity, specificity and false negativity for the combined results of a positive D-dimer test and abnormal ADSF were 100%, 78.0% and 0% for the presence of PE, respectively. Of 65 patients with a low or intermediate clinical probability and a positive D-dimer assay, 36 (55.4%) patients displayed normal ADSF and had no PE. Conclusions By itself ADSF assessment performed well in diagnosis of PE. The combined result of a positive D-dimer and abnormal ADSF increased the specificity for diagnosing PE compared with the D-dimer test alone. The use of additional bedside ADSF assessment following a positive D-dimer test may reduce the need for further imaging studies to detect PE in patients with a low or intermediate clinical probability.

Haemophilus aphrophilus is an aerobic, gram-negative oropharyngeal bacterium, commonly isolated from cases of HACEK endocarditis. In addition, H. aphrophilus has also been shown to cause invasive bone and joint infections. Although multiple cases of H. aphrophilus endocarditis have been described, no cases of invasive bone and joint infections caused by H. aphrophilus have been reported in Korea. Here we report the case of a 69-year old woman with a diagnosis of vertebral osteomyelitis and spinal epidural abscess with compressive myelopathy caused by H. aphrophilus, in which there was no objective evidence of infective endocarditis. She was successfully treated with intravenous administration of cefotaxime and drainage of the epidural abscess by laminectomy of the T3-7 vertebrae. (Korean J Med 2014;86:515-518)

Iatrogenic femoral artery pseudoaneurysm is a complication in patients undergoing catheterization. The risk increased when large-bore sheaths, concomitant anticoagulation therapy, and antiplatelet therapy are used during the intervention. Ultrasound-guided thrombin injection has become the treatment of choice. Rapid expansion, rupture, infection, and mass effect resulting in distal or cutaneous ischaemia or peripheral neuropathy, as well as failure of other treatment options are all indications for surgery. We report a 48-yearold man who developed hemorrhagic shock due to femoral pseudoaneurysm rupture after coronary angiography, and successfully treated by ultrasound-guided thrombin injection.

Objective. The aim of this study was to examine how many Korean rheumatoid arthritis (RA) patients fulfilling the 2008 American College of Rheumatology (ACR) recommendation, 2007 British Society for Rheumatology (BSR) guideline and 2010 Japan College of Rheumatology (JCR) guideline for TNF-α blocker, meet the Korean National Health Insurance reimbursement criteria and to evaluate the reasons for failing the Korean National Health Insurance reimbursement criteria. Methods. Data were obtained from a registry of RA patients who visited rheumatology clinics of Hallym university affiliated hospitals. Patients who were previously prescribed with methotrexate or leflunomide for more than 3 months and had at least one DAS28 examination were included in the present study. Results. Of 642 patients included, 118 episodes meeting ACR guideline for using TNF-α blocker were identified in 88 patients (13.7%). In addition, 19 episodes meeting BSR guideline in 17 patients (2.6%) and 21 episodes meeting JCR guideline in 21 patients (6.2%) were identified. Four episodes (4.8%) meeting ACR recommendation, 0 episodes meeting BSR criteria and 5 episodes (12%) meeting JCR criteria, respectively, were eligible for TNF-α blocker according to the Korean National Health Insurance reimbursement guideline. The most common reason for failing the Korean National Health Insurance reimbursement criteria was the number of active joint counts (92.6%). Conclusion. Our results show that the majority of RA patients satisfying the ACR guideline, BSR and JCR guideline for use of the TNF-α blocker did not meet the Korean National Health Insurance reimbursement criteria. Patients most often failed due to active joint count criteria.