ABSTRACT
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.
Subject(s)
Biosimilar Pharmaceuticals , Circulating Tumor DNA , Stomach Neoplasms , Female , Humans , Male , Middle Aged , Biosimilar Pharmaceuticals/adverse effects , Circulating Tumor DNA/genetics , Gemcitabine , Irinotecan , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Trastuzumab/adverse effects , Adult , Aged , Aged, 80 and overABSTRACT
OBJECTIVE: This study aimed to analyse surgical outcomes of paediatric patients with congenital cholesteatoma according to age. METHOD: This was a retrospective study reviewing the records of 186 children (136 boys and 50 girls) from August 1993 to January 2016. Patients were divided into three age groups (equal to or less than 3 years, over 3 and less than 7 years, and 7 to 15 years). RESULTS: There were significant differences in chief complaints, location of cholesteatoma in the middle ear, computed tomography findings, operation methods, ossicular erosion and type of cholesteatoma sac among the three groups. In addition, older age, open type cholesteatoma, ossicular erosion and mastoid invasion of cholesteatoma increased the recurrence rate after surgery. However, despite higher pre-operative air-bone gap in older children, hearing can be improved enough after proper surgery with ossicular reconstruction. CONCLUSION: Delayed detection of paediatric cholesteatoma can lead to extensive disease and the need for an aggressive operation, which can result in worse hearing outcomes and an increased recurrence risk.
Subject(s)
Cholesteatoma, Middle Ear , Cholesteatoma , Male , Female , Humans , Child , Child, Preschool , Cholesteatoma, Middle Ear/diagnostic imaging , Cholesteatoma, Middle Ear/surgery , Retrospective Studies , Treatment Outcome , Cholesteatoma/surgery , Ear, Middle , Mastoid/diagnostic imaging , Mastoid/surgeryABSTRACT
BACKGROUND: We investigated the feasibility of early line-probe assay (LPA) using remnant DNA of Mycobacterium tuberculosis from polymerase chain reaction (PCR) test.METHODS: M. tuberculosis DNA specimens with cycle threshold (Ct) values reported and collected from patients with known results for both LPA with culture isolates and phenotype drug susceptibility testing (pDST) were selected. The diagnostic performance of DNA-based LPA according to the Ct value was investigated.RESULTS: A total of 143 respiratory specimens were included. For isoniazid resistance, the accuracy in subgroups with Ct value <25, 25-29 and ≥29 was respectively 96.8%, 65.7% and 13.3%. For rifampicin resistance, accuracy in subgroups with Ct values <29 and ≥29 was respectively 87.8% and 13.3%. When compared to the pDST results, sensitivity, specificity, positive predictive value and negative predictive value in specimens with Ct values <25 was respectively 1.00 (95% CI 0.69-1.00), 0.95 (95% CI 0.76-1.00), 0.91 (95% CI 0.59-1.00) and 1.00 (95% CI 0.83-1.00) for isoniazid resistance. For rifampicin resistance, corresponding values in subgroups with Ct values <29 were respectively 0.89 (95% CI 0.52-1.00), 0.98 (95% CI 0.91-1.00), 0.80 (95% CI 0.50-0.94) and 0.99 (95% CI 0.92-1.00).CONCLUSIONS: DNA-based early LPA with remnant DNA from respiratory samples was feasible and accurate when the Ct values were low.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , DNA , Humans , Isoniazid/pharmacology , Isoniazid/therapeutic use , Microbial Sensitivity Tests , Mycobacterium tuberculosis/genetics , Rifampin/pharmacology , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapyABSTRACT
BACKGROUND: Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed and cisplatin combination therapy in patients with refractory bone and soft tissue sarcoma (STS). PATIENTS AND METHODS: Patients were included in this multicenter, phase II study (ClinicalTrials.gov identifier NCT03809637) if they progressed after receiving one or more chemotherapy regimens containing an anthracycline and/or ifosfamide. Pemetrexed was first administered intravenously, followed by cisplatin, over a cycle of 21 days, for a maximum of six cycles. The primary endpoint was a progression-free rate (PFR) at 3 months (3-month PFR). RESULTS: From January 2017 to September 2019, we enrolled 37 patients; of these, 73% had previously undergone three or more rounds of chemotherapy. Five patients (13.5%) exhibited objective responses, including two patients (2/6, 33.3%) with malignant peripheral nerve sheath tumors, one patient (1/4, 25%) with synovial sarcoma, one patient (1/4, 25%) with undifferentiated pleomorphic sarcoma, and one patient (1/4, 25%) with angiosarcoma. The median progression-free survival was 2.6 months, and the 3-month PFR was 45.9% (n = 17). None of the four patients with osteosarcoma exhibited objective responses or were progression free at 3 months. The most frequent treatment-related grade 3-4 toxicities included neutropenia (16.2%), anemia (13.5%), thrombocytopenia (13.5%), and fatigue (8.1%). Among 26 patients (70.3%) available for immunohistochemical assessments, patients in the low-excision repair cross-complementation group 1 (ERCC1) and low-thymidylate synthase expression groups showed a tendency for longer overall survival. CONCLUSIONS: Combination therapy with pemetrexed and cisplatin was associated with clinically meaningful and sustained responses among patients with advanced and refractory STS. The combination therapy met its predefined primary study endpoint.
Subject(s)
Sarcoma , Soft Tissue Neoplasms , Cisplatin/adverse effects , Humans , Ifosfamide , Pemetrexed/adverse effects , Sarcoma/drug therapy , Soft Tissue Neoplasms/drug therapyABSTRACT
BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.
Subject(s)
Breast Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Deoxycytidine/analogs & derivatives , Equilibrative Nucleoside Transporter 1 , Female , Furans , Humans , Ketones , Nuclear Proteins/therapeutic use , Paclitaxel/therapeutic use , Pharmacogenomic Testing , Polymorphism, Genetic , Prospective Studies , Repressor Proteins/therapeutic use , GemcitabineABSTRACT
This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in µ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.
Subject(s)
Bone Resorption , Osteoclasts , Animals , Cell Differentiation , Female , Lactobacillus , Mice , NF-kappa BSubject(s)
Betacoronavirus , Communicable Disease Control/standards , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Practice Guidelines as Topic , Primary Prevention/standards , COVID-19 , Coronavirus Infections/epidemiology , Humans , Pneumonia, Viral/epidemiology , Republic of Korea/epidemiology , SARS-CoV-2ABSTRACT
Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). INTRODUCTION: Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. METHODS: A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. RESULTS: IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). CONCLUSIONS: Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Osteoporotic Fractures/drug therapy , Spinal Fractures/drug therapy , Acute Disease , Aged , Aged, 80 and over , Anabolic Agents/administration & dosage , Female , Fracture Healing/drug effects , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Osteoporosis/drug therapy , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/pathology , Radiography , Retrospective Studies , Risk Factors , Spinal Fractures/diagnostic imaging , Spinal Fractures/pathologyABSTRACT
BACKGROUND: The tip of the tracheal tube should lie at the mid-tracheal level after tracheal intubation in paediatric patients. Auscultation does not guarantee optimal positioning of the tracheal tube. We compared auscultation and the ultrasound-guided lung sliding sign to confirm optimal positioning of the tracheal tube in paediatric patients. METHODS: We studied 74 paediatric patients aged 0-24 months of ASA physical status 1-3 who were scheduled for elective surgery under general anaesthesia. All were randomly assigned to one of two groups: depth of tracheal tube confirmed by auscultation (Group A) or using the ultrasound-guided lung sliding sign (Group S). RESULTS: Optimal positioning of the tracheal tube was observed in 32 of 37 (87%) subjects in Group S and 24 of 37 (65%) subjects in Group A (difference in proportion, 22%; 95% confidence interval, 2-39%; P=0.030). Optimal depth correlated with patient height (adjusted coefficient=0.888, P<0.001). CONCLUSIONS: In paediatric patients younger than 24 months, use of the ultrasound-guided lung sliding sign was more accurate than auscultation for optimal positioning of the tracheal tube. CLINICAL TRIAL REGISTRATION: KCT 0003015.
Subject(s)
Intubation, Intratracheal/methods , Trachea/diagnostic imaging , Ultrasonography, Interventional/methods , Anesthesia, General/methods , Auscultation , Body Height , Double-Blind Method , Elective Surgical Procedures , Female , Humans , Infant , Infant, Newborn , Lung/diagnostic imaging , Male , Prospective StudiesABSTRACT
It has been previously reported that adenovirus 36 (Ad36) infection is associated with obesity in humans and other animals. However, there is no clinically available standard protocol to detect Ad36 DNA. In this study, we developed a method for quantitative and rapid detection of Ad36 DNA. Using a TaqMan probe quantitative polymerase chain reaction (qPCR), we identified that the E3 and E4orf1 regions specifically detect Ad36 DNA, because these regions did not show cross reactivity with other types of adenoviruses. The limit of detection was 379 copy/ml and 384 copy/ml for E3 and E4orf1 regions of Ad36, respectively. The %CV (coefficient of variation) for reproducibility of the assay using adenovirus reference material ranged from 1.07-13.02. After we developed the standard protocol to detect Ad36 DNA, we used mouse as a surrogate model to confirm its clinical applicability. We administered Ad36 to mice via intranasal and oral routes, with intraperitoneal administration as the positive control, to analyze the effect of infection route. Ad36 DNA could be detected in lungs, liver, pancreas, and epididymal fat tissue after intraperitoneal injection, whereas it was found only in lungs after intranasal injection. No Ad36 DNA was detectable in any tested organ after oral injection. This indicates that the main route of infection with Ad36 is intranasal, suggesting that Ad36 is a respiratory virus. The standard protocol for qPCR developed in this study is useful for clinical detection of Ad36 DNA. Keywords: adenovirus 36; real-time PCR; obesity.
Subject(s)
Adenoviridae Infections , Adenoviridae , Obesity , Polymerase Chain Reaction , Adenoviridae/genetics , Adenoviridae Infections/virology , Animals , Humans , Mice , Obesity/virology , Reproducibility of ResultsABSTRACT
We report a new Li-S cell concept based on an optimized F-free catholyte solution and a high loading nanostructured C/S composite cathode. The Li2 S8 present in the electrolyte ensures both buffering against active material dissolution and Li+ conduction. The high S loading is obtained by confining elemental S (≈80 %) in the pores of a highly ordered mesopores carbon (CMK3). With this concept we demonstrate stabilization of a high energy density and excellent cycling performance over 500â cycles. This Li-S cell has a specific capacity that reaches over 1000â mA h g-1 , with an overall S loading of 3.6â mg cm-2 and low electrolyte volume (i.e., 10â µL cm-2 ), resulting in a practical energy density of 365â Wh kg-1 . The Li-S system proposed thus meets the requirements for large scale energy storage systems and is expected to be environmentally friendly and have lower cost compared with the commercial Li-ion battery thanks to the removal of both Co and F from the overall formulation.
ABSTRACT
BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period. RESULTS: Of 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59-1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ. CONCLUSIONS: Final safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149524); EudraCT (2013-004172-35).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/immunology , Breast Neoplasms/mortality , Neoadjuvant Therapy/mortality , Adolescent , Adult , Aged , Biosimilar Pharmaceuticals/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Docetaxel/administration & dosage , Double-Blind Method , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Middle Aged , Prognosis , Survival Rate , Trastuzumab/administration & dosage , Young AdultABSTRACT
GABAergic interneurons regulate the degree of glutamatergic excitation and output of projection neurons. In this study, we investigated the distribution of calbindinD-28k (CB) and parvalbumin (PV) in the somatosensory area of the pigeon pallium using immunohistochemical method. Our results show that anatomical structures of the somatosensory area of the pigeon pallium consisted of several subdivisions including the hyperpallium, intercalated hyperpallium, mesopallium, nidopallium and basorostralis. Neuronal density was significantly higher in the intercalated hyperpallium and basorostralis than that in the other subdivisions. The density of the CB immunoreactive neurons was generally similar in all the subdivisions; however, the density of PV immunoreactive neurons was particularly prominent in the basorostralis compared with that in the other subdivisions. In addition, the mean proportion of PV immunoreactive neurons to total neurons was higher than that in the CB immunoreactive neurons in all the subdivisions. In brief, our present study shows that PV immunoreactive neurons in the somatosensory area of the pigeon pallium were significantly abundant compared with CB immunoreactive neurons. This finding needs more studies regarding CB- and PV-related functions in the somatosensory area of the avian pallium.
Subject(s)
Calbindin 1/metabolism , Columbidae/metabolism , Neurons/metabolism , Parvalbumins/metabolism , Somatosensory Cortex/metabolism , Animals , Benzoxazines , Cell Count/veterinary , Coloring Agents , Gray Matter/cytology , Gray Matter/metabolism , Immunohistochemistry/veterinary , Male , Neurons/cytology , Somatosensory Cortex/cytology , Telencephalon/cytology , Telencephalon/metabolism , White Matter/cytology , White Matter/metabolismABSTRACT
INTRODUCTION: Partial meniscectomy has been preferred in the treatment of discoid lateral meniscus (DLM) with tear, rather than total or subtotal meniscectomy, which could lead to late radiographic degenerative changes. HYPOTHESIS: One or more risk factors contribute to radiographic progression of osteoarthritis after partial meniscectomy of DLM tear. MATERIAL AND METHODS: Inclusion criteria were consecutive patients who underwent arthroscopic surgeries for DLM tear from January 2005 to December 2010 by one surgeon. Exclusion criteria were preoperative osteoarthritis with KL grade 3 or more, osteochondritis dissecans, minimal width of meniscal remnant less than 6mm after meniscectomy, meniscal repair of an unstable discoid meniscus, age over 60years, loss to follow-up for a minimum of 5years and simultaneous surgery on articular cartilage or anterior cruciate ligament. According to the KL grade at the last follow-up, all enrolled knees were sorted into no progression to knee osteoarthritis (KL grade 1 or 2 - NOA) and progression to osteoarthritis (KL grade 3 or 4 - POA) groups. Multivariate logistic regression was used to analyze the risk factors of high-grade osteoarthritis. RESULTS: In comparison with NOA group (n=135) and POA group (n=67), prolonged symptom duration, increased relative percentage of DLM thickness (RPDT) and the presence of horizontal tear were significant risk factors. The presence of horizontal tear (P=0.048, adjusted OR=19.364) was the strongest predictor, compared with prolonged symptom duration (P=0.030, adjusted OR=1.150) and increased RPDT (P=0.003, adjusted OR=1.377). DISCUSSION: Horizontal tear, prolonged symptom duration, and increased RPDT are significant risk factors for radiographic progression to high-grade osteoarthritis after partial meniscectomy of DLM tear with a minimum follow-up of 5years. LEVEL OF EVIDENCE: III, case-control study.
Subject(s)
Menisci, Tibial/diagnostic imaging , Menisci, Tibial/surgery , Osteoarthritis, Knee/diagnostic imaging , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgery , Adolescent , Adult , Arthroscopy , Case-Control Studies , Child , Disease Progression , Female , Humans , Male , Meniscectomy/adverse effects , Menisci, Tibial/abnormalities , Middle Aged , Osteoarthritis, Knee/etiology , Risk Factors , Tibial Meniscus Injuries/complications , Young AdultABSTRACT
Few studies regarding the anatomical distribution of motor neurons innervating muscles of the arm have been demonstrated in avian brains. The purpose of this study was to finely determine the localization of cerebral neurons innervating the biceps brachii muscle in the pigeon. The cholera toxin B subunit (CTB) was employed as a retrograde tracer to determine the location of neurons controlling the biceps brachii muscle in the telencephalon following intramuscular injection in male pigeons (n = 7), which were killed 14 days after intramuscular injection with CTB. We found that CTB-labelled neurons were located contralaterally in the hyperpallium apicale of the rostral telencephalon and that most of the CTB-labelled neurons were pyramidal in shape. This study shows that CTB is easily taken up by nerve terminals which innervate the biceps brachii muscle of the pigeon and that cerebral motor neurons controlling the biceps brachii muscle are located in the hyperpallium apicale.
Subject(s)
Columbidae/anatomy & histology , Muscle, Skeletal/innervation , Neurons/cytology , Telencephalon/cytology , Wings, Animal/innervation , Animals , Benzoxazines , Cholera Toxin , Coloring Agents , Columbidae/physiology , Male , Muscle, Skeletal/cytology , Muscle, Skeletal/physiology , Wings, Animal/cytology , Wings, Animal/physiologyABSTRACT
BACKGROUND: Unicompartmental knee arthroplasty (UKA) is a good alternative treatment option to total knee arthroplasty (TKA) for single compartment knee osteoarthritis. Several recent reports suggest that UKA results in more rapid functional recovery than TKA, together with fewer complications. Few performed a comparison of bilateral simultaneous UKA and unilateral TKA. HYPOTHESIS: Bilateral simultaneous UKA would result in fewer perioperative complications, less blood loss, less transfusion and faster recovery of short-term clinical outcomes, compared with unilateral TKA patients. MATERIAL AND METHODS: In a retrospective trial, the bilateral simultaneous UKA (bUKA) cases were matched one to one with a cohort of unilateral TKA (uTKA) cases according to age, body mass index, gender, Kellgren-Lawrence grade of knee osteoarthritis and American Society of Anesthesiologists score. In bilateral simultaneous UKA group, patients had KL grade 4 of bilateral knee osteoarthritis, and in unilateral TKA group, patients had KL grade 4 of unilateral knee osteoarthritis. The transfusion requirements, estimated blood loss (EBL), duration of hospital stay, incidence of complications, and knee clinical scores of the bUKA and uTKA groups were compared at the 6-month short-term follow-up. RESULTS: Patients were categorized into the bUKA group (n=52) and uTKA group (n=52). The number of patients requiring transfusion and the amount of EBL was smaller in the bUKA group (P<0.001 for transfusion and P=0.043 for EBL). The duration of hospital stay was shorter and the number of complications was smaller in the bUKA group (P<0.001 for hospital stay and P=0.028 for complications). The clinical outcomes were also superior in the bUKA group (P<0.001). CONCLUSIONS: Bilateral simultaneous UKA shows fewer perioperative complications, less blood loss, less transfusion, and better functional outcomes at 6 months postoperatively than unilateral TKA. The data suggest that bilateral simultaneous UKA can be performed safely, and results in acceptable clinical outcomes. LEVEL OF EVIDENCE: III, case-control study.
Subject(s)
Arthroplasty, Replacement, Knee/methods , Hemiarthroplasty/methods , Osteoarthritis, Knee/surgery , Aged , Aged, 80 and over , Blood Loss, Surgical/statistics & numerical data , Blood Transfusion/statistics & numerical data , Case-Control Studies , Female , Follow-Up Studies , Humans , Intraoperative Complications/epidemiology , Intraoperative Complications/etiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Recovery of Function , Retrospective Studies , Treatment OutcomeABSTRACT
RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.
Subject(s)
Breast/metabolism , Cell Transformation, Neoplastic/genetics , Epigenesis, Genetic , RNA Polymerase III/metabolism , Transcription, Genetic , Breast/cytology , Cells, Cultured , Chromatin/genetics , Chromatin/metabolism , DNA/genetics , DNA/metabolism , DNA Methylation , Epithelial Cells/metabolism , Humans , Protein Binding , Proto-Oncogene Proteins c-myc/genetics , RNA, Untranslated/geneticsABSTRACT
AIMS: To investigate whether preoperative magnetic resonance imaging (MRI) in patients with primary breast cancer is predictive of disease-free (DFS) and overall survival and to determine the prognostic factors indicating survival. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. From 2009 to 2010, 828 women with primary breast cancer and preoperative MRI were matched with 1613 women without such imaging. Patients were matched with regards to 25 patient and tumour-related covariates. A Cox proportional hazards model was used to investigate the time to recurrence and to estimate the hazard ratio for preoperative MRI. Log-rank tests and Cox proportional hazards survival analysis were carried out on total recurrence DFS and overall survival in the unmatched datasets. RESULTS: In total, 799 matched pairs were available for survival analysis. The MRI group showed a tendency towards better survival outcome; however, there were no significant differences in DFS and overall survival. Age at diagnosis (DFS hazard ratio = 0.98; overall survival hazard ratio = 1.04), larger tumour size (DFS hazard ratio = 1.01; overall survival hazard ratio = 1.02), triple negative breast cancer (DFS hazard ratio = 2.64; overall survival hazard ratio = 3.44) and the presence of lymphovascular invasion (DFS hazard ratio = 2.12; overall survival hazard ratio = 2.70) were independent significant variables for worse DFS and overall survival. CONCLUSION: Preoperative MRI did not result in an improvement in a patient's outcome. Age at diagnosis, tumour size, molecular subtype and lymphovascular invasion were significant independent factors affecting both DFS and overall survival.
Subject(s)
Breast Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cohort Studies , Disease-Free Survival , Female , Humans , Middle Aged , Retrospective Studies , Survival AnalysisABSTRACT
BACKGROUND: The lower superior vena cava (SVC), near its junction with the right atrium (RA), is considered the ideal location for the central venous catheter tip to ensure proper function and prevent injuries. We determined catheter insertion depth with a new formula using the sternoclavicular joint and the carina as radiological landmarks, with a 1.5 cm safety margin. The accuracy of tip positioning with the radiological landmark-based technique (R) and Peres' formula (P) was compared using transoesophageal echocardiography. METHODS: Real-time ultrasound-guided central venous catheter insertion was done through the right internal jugular or subclavian vein. Patients were randomly assigned to either the P group (n=93) or the R group (n=95). Optimal catheter tip position was considered to be within 2 cm above and 1 cm below the RA-SVC junction. Catheter tip position, abutment, angle to the vascular wall, and flow stream were evaluated on a bicaval view. RESULTS: The distance from the skin insertion point to the RA-SVC junction and determined depth of catheter insertion were more strongly correlated in the R group [17.4 (1.2) and 16.7 (1.5) cm; r=0.821, P<0.001] than in the P group [17.3 (1.2) and 16.4 (1.1) cm; r=0.517, P<0.001], with z=3.96 (P<0.001). More tips were correctly positioned in the R group than in the P group (74 vs 93%, P=0.001). Abutment, tip angle to the lateral wall >40°, and disrupted flow stream were comparable. CONCLUSIONS: Catheter tip position was more accurate with a radiological landmark-based technique than with Peres' formula. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp KCT0001937.