ABSTRACT
BACKGROUND: Step-off deformity is a suboptimal aesthetic outcome at the donor site following abdominal flap harvesting for breast reconstruction. This study assessed the prevalence of step-off deformities post-autologous breast reconstruction and explored the associated risk factors. METHODS: This retrospective study evaluated step-off deformities among consecutive patients who had undergone autologous abdominal flap-based breast reconstruction between January 2019 and December 2022. The postoperative evaluation utilized medical records and photos, defining step-off deformity as a thickness discrepancy in the upper and lower abdominal tissue with reference to the scar line and angles <165°. Moreover, we explored potential risk factors, including abdominal subcutaneous tissue thickness based on computed tomography. RESULTS: In total, 187 patients underwent abdominal flap-based breast reconstruction; 38 exhibited step-off deformity. The case group exhibited significantly higher body mass index (BMI) and greater subcutaneous layer thickness in both the upper and lower abdomen compared to those of the control group. The groups did not differ significantly in postoperative complications, including abdominal bulging or hernia. Multivariable analysis revealed notable risk factors for step-off deformity development: BMI (p=0.026), presence of preoperative abdominal fold (p=0.028) and thickness differences between the upper and lower abdomen (p=0.011). The cut-off values were 26.1 kg/m2 for BMI and 9.5 mm for thickness differences. CONCLUSIONS: Higher BMI, presence of abdominal fold, and significant upper-lower abdomen tissue thickness differences may be associated with an increased risk of donor step-off deformity after abdominal flap harvest. Our findings may inform patient counseling and warrant attention when closing donor wounds in high-risk individuals.
ABSTRACT
Excessive secretion of pro-inflammatory cytokines leads to the disruption of intestinal barrier in inflammatory bowel disease (IBD). The inflammatory cytokine tumor necrosis factor alpha (TNFα) induces the assembly of the NLRP3 inflammasome, resulting in the augmented secretion of inflammatory cytokines implicated in the pathogenesis of inflammatory bowel disease (IBD). TNFα has also been known to induce the formation of immunoproteasome (IP), which incorporates immunosubunits LMP2, LMP7, and MECL-1. Inhibition of IP activity using the IP subunit LMP2-specific inhibitor YU102, a peptide epoxyketone, decreased the protein levels of NLRP3 and increased the K48-linked polyubiquitination levels of NLRP3 in TNFα-stimulated intestinal epithelial cells. We observed that inhibition of IP activity caused an increase in the protein level of the ubiquitin E3 ligase, tripartite motif-containing protein 31 (TRIM31). TRIM31 facilitated K48-linked polyubiquitination and proteasomal degradation of NLRP3 with an enhanced interaction between NLRP3 and TRIM31 in intestinal epithelial cells. In addition, IP inhibition using YU102 ameliorated the symptoms of colitis in the model mice inflicted with dextran sodium sulfate (DSS). Administration of YU102 in the DSS-treated colitis model mice caused suppression of the NLRP3 protein levels and accompanied inflammatory cytokine release in the intestinal epithelium. Taken together, we demonstrated that inhibiting IP under inflammatory conditions induces E3 ligase TRIM31-mediated NLRP3 degradation, leading to attenuation of the NLRP3 inflammatory response that triggers disruption of intestinal barrier.
Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Proteasome Endopeptidase Complex , Tripartite Motif Proteins , Ubiquitin-Protein Ligases , Ubiquitination , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Animals , Ubiquitin-Protein Ligases/metabolism , Tripartite Motif Proteins/metabolism , Inflammasomes/metabolism , Proteasome Endopeptidase Complex/metabolism , Mice , Humans , Ubiquitination/drug effects , Mice, Inbred C57BL , Colitis/chemically induced , Colitis/pathology , Colitis/metabolism , Colitis/immunology , Tumor Necrosis Factor-alpha/metabolism , Dextran Sulfate , Disease Models, AnimalABSTRACT
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), had a major impact on both the global health and economy. Numerous virus-neutralizing antibodies were developed against the S1 subunit of SARS-CoV-2 spike (S) protein to block viral binding to host cells and were authorized for control of the COVID-19 pandemic. However, frequent mutations in the S1 subunit of SARS-CoV-2 enabled the emergence of immune evasive variants. To address these challenges, broadly neutralizing antibodies targeting the relatively conserved S2 subunit and its epitopes have been investigated as antibody therapeutics and universal vaccines. Methods: We initiated this study by immunizing BALB/c mice with ß-propiolactone-inactivated SARS-CoV-2 (IAV) to generate B-cell hybridomas. These hybridomas were subsequently screened using HEK293T cells expressing the S2-ECD domain. Hybridomas that produced anti-S2 antibodies were selected, and we conducted a comprehensive evaluation of the potential of these anti-S2 antibodies as antiviral agents and versatile tools for research and diagnostics. Results: In this study, we present a novel S2-specific antibody, 4A5, isolated from BALB/c mice immunized with inactivated SARS-CoV-2. 4A5 exhibited specific affinity to SARS-CoV-2 S2 subunits compared with those of other ß-CoVs. 4A5 bound to epitope segment F1109-V1133 between the heptad-repeat1 (HR1) and the stem-helix (SH) region. The 4A5 epitope is highly conserved in SARS-CoV-2 variants, with a significant conformational feature in both pre- and postfusion S proteins. Notably, 4A5 exhibited broad neutralizing activity against variants and triggered Fc-enhanced antibody-dependent cellular phagocytosis. Discussion: These findings offer a promising avenue for novel antibody therapeutics and insights for next-generation vaccine design. The identification of 4A5, with its unique binding properties and broad neutralizing capacity, offers a potential solution to the challenge posed by SARS-CoV-2 variants and highlights the importance of targeting the conserved S2 subunit in combating the COVID-19.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Mice , Humans , SARS-CoV-2/genetics , Antibodies, Viral , Pandemics , HEK293 Cells , EpitopesABSTRACT
BACKGROUND & AIMS: Chronic rhinosinusitis (CRS) is one of the most prevalent upper respiratory tract diseases. However, little is known the effect of CRS on the cardiovascular aspects of patients. This study aimed to investigate the incidence of acute myocardial infarction (AMI) in patients with CRS compared with that in the general population. METHODS: This retrospective cohort study was performed using the Korean National Health Insurance Service (NHIS) database. To minimize confounding, age, sex, and cardiovascular risk profiles were adjusted. The primary endpoint was newly diagnosed AMI in patients between January 2005 and December 2018. The relative risk of AMI in patients with CRS was compared with that in controls. Kaplan-Meier survival curves and Cox proportional regression tests were used for statistical analyses. RESULTS: Among 5,179,981 patients from the NHIS database, 996,679 patients with CRS were selected. The control group was 10 times (n = 9,966,790) the number of individuals in the CRS group. The CRS group had better cardiovascular profiles than those of the control group and had an adjusted hazard ratio of 0.99 (95% confidence interval, 0.97-1.02) for AMI. CONCLUSION: There was no significant association between the two groups regardless of the presence of nasal polyps. This is the first study adjusting cardiovascular risk profiles and analyzing the relationship between CRS and AMI. CRS was not associated with a high incidence of AMI after adjusting for cardiovascular risk factors.
Subject(s)
Myocardial Infarction , Sinusitis , Humans , Incidence , Retrospective Studies , Myocardial Infarction/epidemiology , Sinusitis/complications , Sinusitis/epidemiology , Research Design , Chronic DiseaseABSTRACT
Influenza A virus continuously infects humans and the antigenic shifts of this respiratory virus enable it to cross the species barrier, threatening public health with the risk of pandemics. Broadly neutralizing antibodies (bnAbs) that target the antigenic surface glycoprotein, hemagglutinin (HA), of influenza A virus protect against various subtypes of the virus. Here, we screened a human scFv library, through phage display and panning against recombinant HA proteins, to discover human monoclonal antibodies (mAbs) that are broadly active. Consequently, two human mAbs, named G1 and G2, were identified, which target the HA proteins of the H1N1 and H3N2 subtypes, respectively. G1 was shown to have broad binding ability to different HA subtypes of group 1. By contrast, G2 had higher binding affinity but sensed exclusively H3 subtype-derived HAs. In a cell culture-based virus-neutralizing assay, both G1 and G2 efficiently suppressed infection of the parental influenza A viruses of H1N1 and H3N2 subtypes. Mode-of-action studies showed that the G1 antibody blocked HA2-mediated membrane fusion. Meanwhile, G2 inhibited HA1-mediated viral attachment to host cells. It is noteworthy that both antibodies elicited antibody-dependent cellular cytotoxicity (ADCC) activities by recruiting FcγRIIIA-expressing effector cells. In mouse challenge models, single-shot, intraperitoneal administration of chimeric G1 and G2 antibodies with the mouse IgG constant region completely protected mice from viral infections at doses above 10 and 1 mg/kg, respectively. The newly identified bnAbs, G1 and G2, could provide insight into the development of broad-spectrum antivirals against future pandemic influenza A virus involving group 1- or H3-subtyped strains.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza Vaccines , Influenza, Human , Humans , Animals , Mice , Antibodies, Neutralizing , Broadly Neutralizing Antibodies , Antibodies, Viral , Influenza A Virus, H3N2 Subtype , Hemagglutinin Glycoproteins, Influenza Virus , Antibodies, Monoclonal , HemagglutininsABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancer, causing considerable mortality and morbidity worldwide. Although HNSCC management has been extensively studied, the treatment outcomes have not improved - the 5-year survival rate of patients with HNSCC is 40%. Recent studies on the development of a novel HNSCC treatment have highlighted proto-oncogene tyrosine-protein kinase Src (c-Src) as one of the major therapeutic targets. However, the clinical efficacy of c-Src inhibitors against HNSCC was not comparable to that obtained in vitro. Furthermore, the molecular mechanisms underlying the efficacy of c-Src inhibitors remain elusive. In this study, we assessed the efficacy of 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d] pyrimidine (PP2), a selective c-Src inhibitor on HSNCC. Nine HNSCC cell lines (SNU1041, Fraud, SNU46, SNU1076, SNU899, SCC1483, YD15, YD9, and YD10-) were screened, and the effects of PP2 were evaluated using wound healing, apoptosis, and invasion assays. Western blot analysis of downstream markers was conducted to assess the specific mechanism of action of PP2 in HNSCC. The therapeutic efficacy of PP2 was further evaluated in xenograft mice. PP2 reduced tumor cell growth both in vitro and in vivo. Furthermore, it enhanced tumor cell apoptosis in cell lines and prevented metastasis in mice. PP2 also regulated the epithelial-mesenchymal transition pathway downstream of c-Src. More specifically, in SCC1483 and YD15PP2 HNSCC cell lines, PP2 exposure downregulated Erk, Akt/Slug, and Snail but upregulated E-cadherin. These results suggest that PP2 inhibits cell growth and progression in HNSCC by regulating the epithelial-mesenchymal transition pathway.
Subject(s)
Epithelial-Mesenchymal Transition , Head and Neck Neoplasms , Humans , Animals , Mice , Head and Neck Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Cell Line, Tumor , Cell ProliferationABSTRACT
The implications of nutrient starvation due to aging on the degeneration of the retinal pigment epithelium (RPE) is yet to be fully explored. We examined the involvement of AMPK activation in mitochondrial homeostasis and its relationship with the maintenance of a healthy mitochondrial population and epithelial characteristics of RPE cells under nutrient starvation. Nutrient starvation induced mitochondrial senescence, which led to the accumulation of reactive oxygen species (ROS) in RPE cells. As nutrient starvation persisted, RPE cells underwent pathological epithelial-mesenchymal transition (EMT) via the upregulation of TWIST1, a transcription regulator which is activated by ROS-induced NF-κB signaling. Enhanced activation of AMPK with metformin decelerated mitochondrial senescence and EMT progression through mitochondrial biogenesis, primed by activation of PGC1-α. Thus, by facilitating mitochondrial biogenesis, AMPK protects RPE cells from the loss of epithelial integrity due to the accumulation of ROS in senescent mitochondria under nutrient starvation. [BMB Reports 2023; 56(2): 84-89].
Subject(s)
AMP-Activated Protein Kinases , Oxidative Stress , Reactive Oxygen Species , AMP-Activated Protein Kinases/metabolism , Organelle Biogenesis , Epithelial Cells/metabolism , Retinal Pigments , Retinal Pigment Epithelium/metabolismABSTRACT
We analyzed the relationship between chronic rhinosinusitis (CRS) and the incidence of head and neck cancers (HNCs) in a Korean adult population. This retrospective cohort study included data from the Korean National Health Insurance Service database. Adjustments were made to minimize risk variables for sex, age, diabetes, hypertension, dyslipidemia, and rhinitis between the two groups. The primary endpoint was newly diagnosed HNC between January 2009 and December 2018. Among 1,337,120 subjects in the Korean National Health Insurance Service database, data from 324,774 diagnosed with CRS (CRS group) and 649,548 control subjects (control group) were selected. Patients with CRS exhibited a statistically significant greater risk for nasal cavity/paranasal sinus cancer, hypopharynx/larynx cancer, and thyroid cancer compared with the control group. In the CRS group, the adjusted hazard ratios for nasal cavity/paranasal sinus cancer were 1.809 (95% confidence interval (CI) 1.085-3.016), 1.343 (95% CI 1.031-1.748) for hypopharynx and larynx cancer, and 1.116 (95% CI 1.063-1.173) for thyroid cancer. CRS was associated with a higher incidence of HNCs. Therefore, physicians should carefully consider the possibility of HNC progression and implement therapeutic strategies to minimize the impact of these diseases.
ABSTRACT
The therapeutic efficacy of a protein binder largely depends on two factors: its binding site and its binding affinity. Advances in in vitro library display screening and next-generation sequencing have enabled accelerated development of strong binders, yet identifying their binding sites still remains a major challenge. The differentiation, or "binning", of binders into different groups that recognize distinct binding sites on their target is a promising approach that facilitates high-throughput screening of binders that may show different biological activity. Here we study the extent to which the information contained in the amino acid sequences comprising a set of target-specific binders can be leveraged to bin them, inferring functional equivalence of their binding regions, or paratopes, based directly on comparison of the sequences, their modeled structures, or their modeled interactions. Using a leucine-rich repeat binding scaffold known as a "repebody" as the source of diversity in recognition against interleukin-6 (IL-6), we show that the "Epibin" approach introduced here effectively utilized structural modelling and docking to extract specificity information encoded in the repebody amino acid sequences and thereby successfully recapitulate IL-6 binding competition observed in immunoassays. Furthermore, our computational binning provided a basis for designing in vitro mutagenesis experiments to pinpoint specificity-determining residues. Finally, we demonstrate that the Epibin approach can extend to antibodies, retrospectively comparing its predictions to results from antigen-specific antibody competition studies. The study thus demonstrates the utility of modeling structure and binding from the amino acid sequences of different binders against the same target, and paves the way for larger-scale binning and analysis of entire repertoires.
ABSTRACT
Autophagy is a lysosome-mediated degradative process that removes damaged proteins and organelles, during which autophagosome-lysosome fusion is a key step of the autophagic flux. Based on our observation that intermediate cytofilament keratin 8 (KRT8) enhances autophagic clearance in cells under oxidative stress condition, we investigated whether KRT8 supports the cytoplasmic architectural networks to facilitate the vesicular fusion entailing trafficking onto filamentous tracks. We found that KRT8 interacts with actin filaments via the cytolinker, plectin (PLEC) during trafficking of autophagosome. When PLEC was knocked down or KRT8 structure was collapsed by phosphorylation, autophagosome-lysosome fusion was attenuated. Inhibition of actin polymerization resulted in accumulation of autophagosomes owing to a decrease in autophagosome and lysosome fusion. Furthermore, myosin motor protein was found to be responsible for vesicular trafficking along the actin filaments to entail autolysosome formation. Thus, the autophagosome-lysosome fusion is aided by PLEC-stabilized actin filaments as well as intermediate cytofilament KRT8 that supports the structural integrity of actin filaments during macroautophagic process under oxidative stress condition.
Subject(s)
Actins/metabolism , Autophagosomes/metabolism , Keratin-8/metabolism , Lysosomes/metabolism , Plectin/metabolism , Cell Line , Humans , Membrane Fusion , Protein Interaction MapsABSTRACT
Childhood apraxia of speech (CAS) causes inconstant oromotor production. We investigated the clinical efficacy of repeated urimal test of articulation and phonation (U-TAP) in CAS patients. Twenty-eight children were recruited: 19 with CAS and 9 with functional articulation disorder (FAD). Four age-matched typically developing children were also recruited. U-TAP was performed twice repeatedly, and the error rate of consonant accuracy (CA) was measured. Preschool Receptive-Expressive Language Scale (PRES) was also performed. The mean U-TAP CA showed a significant difference between the three groups, with 42.04% for CAS, 77.92% for FAD, and 99.68% for the normal group (p < 0.05). The mean difference between the two U-TAP CAs was 10.01% for CAS, 0.82% for FAD, and no difference for the normal group, revealing a significant intergroup difference between CAS and FAD (p < 0.05). For the expressive and receptive PRES scores, CAS group showed significantly decreased results compared to FAD and normal group. Only in the CAS group, expressive PRES showed significant decrease rather than receptive PRES score. The CAS group showed a significant difference in the two U-TAP CA compared to the FAD and normal groups. This result implies that repeated U-TAP can be useful for supportive diagnostic tool for CAS by detecting poor reliability of phonation.
ABSTRACT
OBJECTIVES: Predicting the need for surgical treatment among patients with chronic rhinosinusitis (CRS) is challenging. The delta neutrophil index (DNI) has been proposed as a useful laboratory marker of immature granulocytes, which indicates infection or severe inflammation in several diseases. This study evaluated DNI as an early predictor of the need for surgery in patients with CRS. METHODS: A total of 117 patients diagnosed with CRS were enrolled in this retrospective and observational study. Medical records, including symptoms data, WBC count, ESR level, LUC count, Lund-Mackay scores, and DNI, were reviewed. The receiver operating characteristic (ROC) curves were analyzed to determine the optimal cut-off values for predicting surgery. RESULTS: Among 117 patients, 49 patients (41.9%) needed surgical intervention. The areas under the WBC, ESR, LUC, and DNI ROC curves were .571, .600, .592, and .782, respectively. The optimal cut-off value of DNI to predict surgery was .9%. The prognostic precision of DNI showed that the sensitivity was 59.2% and the specificity was 98.5%. In the analysis of risk factors, DNI levels were significantly associated with surgical intervention (odds ratio, 2.22; 95% confidence interval, 1.48-3.34; P < .01). CONCLUSIONS: The level of DNI, which reflects the severity of the disease, may be a useful predictor for determining the need for surgical intervention in patients with CRS. This is the first literature to verify the role of DNI in upper airway disease.
ABSTRACT
Dysregulation of mitochondrial homeostasis and accumulation of damaged mitochondria cause degenerative diseases such as age-related macular degeneration (AMD). We studied the effects of the intermediate cytofilament KRT8 (keratin 8) on mitochondrial homeostasis in relation to the morphology and function of mitochondria in retinal pigment epithelial cells under oxidative stress. When the mitochondria were damaged owing to oxidative stress, the damaged mitochondria were readily disposed of via mitophagy following mitochondrial fission. During this process, KRT8 was found to physically interact with the mitochondria through PLEC (plectin) and facilitate the mitochondrial fission-mediated mitophagy. However, the association between PLEC-anchoring mitochondria and KRT8 was dwindled by KRT8 phosphorylation under oxidative stress. The efficient KRT8-facilitated mitophagy flux suppressed the accumulation of damaged mitochondria and consequently diminished necrotic cell death under oxidative stress. Thus, by facilitating mitophagy, KRT8 protects RPE cells against necrotic cell death due to oxidative stress.Abbreviations: 3-MA: 3-methyladenine; AMD: age-related macular degeneration; DDIT3: DNA damage inducible transcript 3; DNM1L: dynamin 1 like; ER: endoplasmic reticulum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCN1: GCN1 activator of EIF2AK4; IF: intermediate filament; KRT8: keratin 8; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3; MFF: mitochondrial fission factor; MMP: mitochondrial membrane potential; OCR: oxygen consumption rate; PLEC: plectin; ROS: reactive oxygen species; RPE: retinal pigment epithelium; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20.
Subject(s)
Mitochondrial Dynamics , Mitophagy , Autophagy , Cell Death , Keratin-8/metabolism , Mitophagy/genetics , Plectin , Reactive Oxygen Species/metabolismABSTRACT
Complement component 3a (C3a) plays a crucial role in the immune response and host defense, but it is also involved in pro-inflammatory responses, causing many inflammatory disorders. Blockade of C3a has been regarded as a potent therapeutic strategy for inflammatory diseases. Here, we present the development of a human C3a (hC3a)-specific protein binder, which effectively inhibits pro-inflammatory responses. The protein binder, which is composed of leucine-rich repeat modules, was selected against hC3a through phage display, and its binding affinity was matured up to 600 pM by further expanding the binding interface in a module-by-module manner. The developed protein binder was shown to have more than 10-fold higher specificity to hC3a compared with human C5a, exhibiting a remarkable suppression effect on pro-inflammatory response in monocyte, by blocking the interaction between hC3a and its receptor. The hC3a-specific protein binder is likely to have a therapeutic potential for C3a-mediated inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Complement C3a/antagonists & inhibitors , Inflammation/drug therapy , Leucine/analogs & derivatives , Leucine/pharmacology , Cells, Cultured , Complement Activation/drug effects , Complement C3a/immunology , Humans , Inflammation/immunology , Models, MolecularABSTRACT
Immune checkpoint inhibitors have drawn a consider attention as an effective cancer immunotherapy, and several monoclonal antibodies targeting the immune checkpoint receptors, such as human programmed cell death-1 (hPD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), are clinically used for treatment of various cancers. Here we present the development of a small-sized protein binder which specifically binds to hPD-1. The protein binder, which is composed of leucine-rich repeat (LRR) modules, was selected against hPD-1 through phage display, and its binding affinity was maturated up to 17 nM by modular evolution approach. The protein binder was shown to be highly specific for hPD-1, effectively inhibiting the interaction between hPD-1 and its ligand, hPD-L1. The protein binder restored T-cell function in vitro, and exhibited a strong anti-tumour activity in tumour mouse model, indicating that it acts as an effective checkpoint blockade. Based on the results, the developed protein binder specific for hPD-1 is likely to find a potential use in cancer immunotherapy.
Subject(s)
Cell Proliferation/drug effects , Immune Checkpoint Inhibitors/pharmacology , Neoplasms/drug therapy , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/metabolism , Protein Binding/drug effects , Animals , Antibodies, Monoclonal/pharmacology , CHO Cells , CTLA-4 Antigen/metabolism , Cell Line , Cricetulus , Disease Models, Animal , Female , Humans , Immunotherapy/methods , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred NOD , Neoplasms/therapy , T-Lymphocytes/drug effectsABSTRACT
BACKGROUND: The aim of this study was to investigate the prognostic value of preoperative systemic inflammation markers in upper tract urothelial carcinoma (UTUC). METHODS: A total of 1137 patients who underwent radical nephroureterectomy with bladder cuff excision at 9 institutions from 2004 to 2015, were retrospectively reviewed. The Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for each patient were calculated. Univariable and multivariable analysis was performed using the Cox proportional hazards regression model. Cut-off values for NLR and PLR were calculated using a receiver operating characteristic curve. RESULTS: The median follow-up period was 39.1 (interquartile range: 18.3-63.8) months. Univariable analysis revealed that GPS, mGPS, PLR, and NLR (all, P=0.001) were significantly associated with both recurrence-free survival (RFS) and cancer-specific survival (CSS). Multivariable analysis revealed that GPS (P=0.001), PLR (hazards ratio [HR] =1.32; 95% CI: 1.08-1.62, P=0.007 and HR =1.87; 95% CI: 1.21-2.92, P=0.005), NLR (HR =1.38; 95% CI: 1.12-1.69, P=0.003 and HR =1.70; 95% CI: 1.10-2.62, P=0.017) were significantly associated with RFS and CSS. CONCLUSIONS: Our results suggest that preoperative systemic inflammation markers such as GPS, PLR, and NLR are independent prognostic factors in patients with UTUC after surgery.
Subject(s)
Carcinoma, Transitional Cell/diagnosis , Inflammation Mediators/blood , Urologic Neoplasms/diagnosis , Aged , Blood Cell Count , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/surgery , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nephrectomy , Predictive Value of Tests , Prognosis , Retrospective Studies , Survival Analysis , Ureter/surgery , Urologic Neoplasms/blood , Urologic Neoplasms/surgery , Urologic Surgical ProceduresABSTRACT
OBJECTIVES: The aims of this study were to evaluate the role of intra-articular joint injection for atlanto-occipital (AO) joint pain and to determine pain referral sites from that joint. DESIGN: Prospective observational study. METHOD: We evaluated 29 patients with chronic refractory neck pain and/or headache, and limited range of lateral bending with rotation at the AO joint on physical examination. Of the 24 patients who consented to undergo diagnostic injections, 20 patients had at least 50% relief from pain and underwent two AO intra-articular injections of mixture of local anesthetic and steroid approximately 1 week apart. Patients completed pain drawings, visual analog scales (VASs) for pain, and neck disability index (NDI) for level of function. Patients were evaluated for 2 months after the first injection. RESULT: There was headache in 14/20 (70%), posterior neck pain (PNP) in 20, and referred pain in 17 (85%). The average VAS values for headache, PNP, and other referred pains were reduced significantly from 5.64, 5.70, and 5.41, respectively, before treatments to 0.64, 2.30, and 1.71, respectively, two months after injection (P < 0.01). The average NDI value was reduced significantly from 39.95% at pretreatment to 20.40% at 2 months after treatment (P < 0.01). CONCLUSION: AO intra-articular steroid injection appears effective for the short-term control of chronic refractory pain arising from the AO joint.
Subject(s)
Arthralgia/drug therapy , Atlanto-Occipital Joint/drug effects , Pain Measurement/drug effects , Triamcinolone/administration & dosage , Adult , Aged , Arthralgia/diagnostic imaging , Atlanto-Occipital Joint/diagnostic imaging , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Injections, Intra-Articular , Male , Middle Aged , Pain Measurement/methods , Prospective Studies , Radiography , Treatment OutcomeABSTRACT
BACKGROUND: Epiphyseal stapling has been widely used to correct angular deformity. The mechanism, however, has not been well determined. To determine the effect of temporary hemiepiphyseal stapling on the cellular layers of the physis, a histomorphometric study was performed using immature rabbits. METHODS: Distal lateral epiphyseal stapling of the right femur was performed on 6-week-old New Zealand white rabbits. Thirty rabbits were randomly assigned to five groups, and six rabbits in each group were analyzed weekly for up to 5 weeks. RESULTS: The distal femur was deformed into the valgus, and the anatomical lateral distal femoral angle decreased with the passage of time. In the sequential histomorphometry of the operated physeal plate, the area ratio of each layer, compared to the control side, decreased every week. The total area of the physeal plate had decreased up to 60 % at the 5th week compared to the area of the 1st week, and the area of the proliferative layer decreased by the greatest amount among the three layers. CONCLUSIONS: Our findings suggest that the proliferation of chondrocytes seemed to be more suppressed by the compression of the stapling, thereby slowing the growth rate, although hypertrophy of the chondrocytes was also suppressed.