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Objective: This study aimed to demonstrate and characterize a rare cervical spondylotic myelopathy (CSM) with sciatica-like pain as the main clinical manifestation through case presentation and systematic review. Methods: Four cases of CSM with sciatica-like pain as the main clinical manifestation were retrospectively studied. A systematic review of electronic databases such as PubMed, Embase, and Web of Science was conducted to explore the clinical characteristics of CSM with sciatica. Results: All four cases of CSM symptomatic of sciatica-like pain were initially diagnosed with lumbar degenerative conditions. However, due to the presence of neurological signs such as hyperactive tendon reflexes, a positive Babinski sign, or a Hoffmann sign, they underwent further cervical MRI scans. Eventually, all four cases were diagnosed with CSM and experienced relief from sciatica after cervical decompression surgery. The systematic review analyzed a total of four studies with a combined sample size of 10 cases, all of whom experienced a reduction in sciatica-like pain following cervical decompression surgery. Conclusion: CSM symptomized by sciatica-like pain can often be misdiagnosed as lumbar degenerative disease. Preoperative abnormal neurological signs associated with CSM may aid in diagnosing this condition. In addition, the clinical presentation of hyperextension of the cervical spine resulting in worsening lower limb pain may serve as diagnostic indicators for this disease.
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PURPOSE: To analyze the characteristics of PEEK rods retrieved in vivo, specifically their wear and deformation, biodegradability, histocompatibility, and mechanical properties. METHOD: Six PEEK rods were retrieved from revision surgeries along with periprosthetic tissue. The retrieved PEEK rods were evaluated for surface damage and internal changes using Micro-CT, while light and electron microscopy were utilized to determine any histological changes in periprosthetic tissues. Patient history was gathered from medical records. Two intact and retrieved PEEK rods were used for fatigue testing analysis by sinusoidal load to the spinal construct. RESULTS: All implants showed evidence of plastic deformation around the screw-rod interface, while the inner structure of PEEK rods appeared unchanged with no visible voids or cracks. Examining images captured through light and electron microscopy indicated that phagocytosis of macrophages around PEEK rods was less severe in comparison to the screw-rod interface. The results of an energy spectrum analysis suggested that the distribution of tissue elements around PEEK rods did not differ significantly from normal tissue. During fatigue testing, it was found that the retrieved PEEK rods cracked after 1.36 million tests, whereas the intact PEEK rods completed 5 million fatigue tests without any failure. CONCLUSION: PEEK rods demonstrate satisfactory biocompatibility, corrosion resistance, chemical stability, and mechanical properties. Nevertheless, it is observed that the indentation at the junction between the nut and the rod exhibits relatively weak strength, making it susceptible to breakage. As a precautionary measure, it is recommended to secure the nut with a counter wrench, applying the preset torque to prevent overtightening.
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Benzofenonas , Cetonas , Parafusos Pediculares , Polímeros , Humanos , Cetonas/química , Feminino , Masculino , Polietilenoglicóis/química , Pessoa de Meia-Idade , Remoção de Dispositivo , Teste de Materiais , Idoso , Materiais Biocompatíveis , Falha de Prótese , ReoperaçãoRESUMO
To explore the risk factors for residual symptoms following percutaneous endoscopic lumbar discectomy (PELD). A retrospective case-controlled study. From January 2015 to December 2020, consecutive patients who underwent PELD for lumbar disc herniation (LDH) in our department were retrospectively studied. All the patients were followed-up at least two years. Residual symptoms were analyzed for association with baseline data, clinical feature, physical examination, and radiographic characteristics, which were used to detected the risk factors. A total of 339 patients were included in this study, with a mean follow-up of 28.7 ± 3.6 months. Of the enrolled patients, 90 (26.5%) patients experienced residual low back pain (LBP), and 76 (22.4%) patients experienced leg numbness (LN). Multivariate logistic regression analysis revealed that intervertebral disc calcification on CT scans (odd ratio, 0.480; 95% confidence interval: 0.247 ~ 0.932; P < 0.05) was independent risk factor for postoperative residual LBP with odd ratio and longer symptom duration was risk factor for postoperative residual LN (odd ratio, 2.231; 95% confidence interval:1.066 ~ 4.671; P < 0.05). Residual symptoms following transforaminal endoscopic surgery are quite prevalent. Intervertebral disc calcification is a protective factor for residual low back pain, and a longer symptom duration is a risk factor for residual leg numbness.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Dor Lombar , Vértebras Lombares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Discotomia Percutânea/métodos , Adulto , Vértebras Lombares/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Estudos Retrospectivos , Prognóstico , Dor Lombar/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Estudos de Casos e Controles , Fatores de Risco , Endoscopia/métodos , Endoscopia/efeitos adversos , Degeneração do Disco Intervertebral/cirurgia , Calcinose/cirurgia , IdosoRESUMO
The exploration of sonodynamic therapy (SDT) as a possible replacement for antibiotics by creating reactive oxygen species (ROS) is suggested as a non-drug-resistant theranostic method. However, the low-efficiency ROS generation and complex tumor microenvironment which can deplete ROS and promote tumor growth will cause the compromised antibacterial efficacy of SDT. Herein, through an oxygen vacancy engineering strategy, TiO2- x microspheres with an abundance of Ti3+ are synthesized using a straightforward reductant co-assembly approach. The narrow bandgaps and Ti3+/Ti4+-mediated multiple-enzyme catalytic activities of the obtained TiO2- x microspheres make them suitable for use as sonosensitizers and nanozymes. When graphene quantum dot (GQD) nanoantibiotics are deposited on TiO2- x microspheres, the resulting GQD/TiO2- x shows an increased production of ROS, which can be ascribed to the accelerated separation of electron-hole pairs, as well as the peroxidase-like catalytic activity mediated by Ti3+, and the depletion of glutathione mediated by Ti4+. Moreover, the catalytic activities of TiO2- x microspheres are amplified by the heterojunctions-accelerated carrier transfer. In addition, GQDs can inhibit Topo I, displaying strong antibacterial activity and further enhancing the antibacterial activity. Collectively, the combination of GQD/TiO2- x-mediated SDT/NCT with nanoantibiotics can result in a synergistic effect, allowing for multimodal antibacterial treatment that effectively promotes wound healing.
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PURPOSE: After spinal surgery, negative pressure wound treatment (NPWT) improves deep surgical site infection (DSSI) wound healing. This research compared the healing benefits of two sponge implantation strategies in NPWT for DSSI. METHODS: 21 patients with DSSI utilized NPWT to improve wound healing following spine surgery were followed from January 1, 2012 to December 31, 2021. After antibiotic treatment failure, all these patients with DSSI received extensive debridement and NPWT. They are grouped by sponge placement method: centripetal reduction and segment reduction. The two groups' hospital stays, NPWT replacement frequency, wound healing time, healing speed, and quality of wound healing (POSAS score) were compared. RESULTS: All patients had been cured by the end of December 2022, and the mean follow-up time was 57.48 ± 29.6 months. Surgical incision length did not vary across groups (15.75±7.61 vs. 15.46±7.38 cm, P = 0.747). The segmental reduction approach had shorter hospital stay and NPWT treatment times than the centripetal reduction method (39.25±16.04 vs. 77.38±37.24 days, P = 0.027). Although there is no statistically significant difference, the mean wound healing duration of segmental reduction group is faster than that of centripetal reduction group (0.82±0.39 vs 0.45±0.28 cm/d, P = 0.238), wound healing quality (POSAS) (33.54±8.63 vs 48.13±12.17, P = 0.408) is better in segmental reduction group, and NPWT replacement frequency (2.62 ± 1.04 vs 3.88 ± 1.25, P < .915) is smaller in segmental reduction group. CONCLUSIONS: NPWT heals wounds and controls infection. Segmental reduction method accelerates wound healing, reduces hospital stay, and improves wound quality compared to central reduction method.
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Lesões por Esmagamento , Tratamento de Ferimentos com Pressão Negativa , Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Cicatrização , Procedimentos NeurocirúrgicosRESUMO
PURPOSE: Percutaneous endoscopic lumbar discectomy has been increasingly used in the treatment of lumbar disc herniation. However, there is no consensus on which method would be more effective between the transforaminal and interlaminar approach. OBJECTIVE: To compare clinical outcomes, patient satisfaction rate, reoperation rate, and residual symptoms between percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). STUDY DESIGN: A comparative, retrospective, controlled trial. SETTING: The study was conducted at the Department of Orthopaedics at a local hospital. METHODS: From January 2015 to September 2020, consecutive patients who underwent PETD or PEID treatment for lumbar disk herniation (LDH) at the L5/S1 level in our department were retrospectively collected. Baseline data including age, gender, body mass index (BMI), smoking status, alcohol drinking, clinical symptoms, physical examination, and radiographic characteristics were documented. During the two to three year follow-up periods, patients were evaluated clinically, including clinical outcomes assessed by the visual analog score (VAS), patient satisfaction rates assessed by the North American Spine Society patient satisfaction index (PSI), recurrent rate, and residual symptoms. RESULTS: A total of 113 patients with PELD in our department were included in the current study, with 65 patients in the PETD group and 48 in the PEID group. Demographic characteristics including age, gender, height, BMI, cigarette smoking, alcohol consumption status, and diabetes did not show any significant difference between the PETD and PEID groups. The VAS scores of the two groups were similar preoperatively, but the postoperative VAS score of the PEID group was lower than that of the PETD group. There were 90.8% of patients in the PETD group who were satisfied with the operation compared to 97.9% in the PEID group. The recurrence rate did not differ between groups, with three patients in both groups. Regarding residual symptoms, there were more patients in the PETD group who reported low back pain during the follow-up periods. LIMITATION: The main limitations are that all patients were operated by the same surgical team from the same site, and there was a lack of multicenter data. CONCLUSION: Both PETD and PEID have satisfactory patient-reported outcomes for treating LDH. The PEID procedure results in fewer low back pain residual symptoms than the PELD procedure.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Dor Lombar , Humanos , Discotomia/efeitos adversos , Discotomia/métodos , Discotomia Percutânea/efeitos adversos , Discotomia Percutânea/métodos , Endoscopia/efeitos adversos , Endoscopia/métodos , Seguimentos , Deslocamento do Disco Intervertebral/cirurgia , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Purpose: To determine the long-term radiological outcomes of PEEK rods in patients with lumbar degenerative diseases. Methods: Radiological outcomes of cohort cases with lumbar degenerative diseases following PEEK rods were retrospectively studied. Disc height index (DHI) and range of motion (ROM) were measured by x-rays. The CT scans and reconstruction were used to determine screw breakage, rods fracture, screw loosening and intervertebral bony fusion status. The MRI scans were used to evaluate the changes of intervertebral discs at the non-fusion segments and adjacent segments in terms of Pfirrmann Classification. Results: A total of 40 patients completed the mean of 74.8 ± 9.6 months follow-up, with 32 patients undergoing hybrid surgery and 8 patients undergoing non-fusion surgery. The mean DHI changed from preoperative 0.34 to 0.36 at the final follow-up and the ROM declined from 8.8° preoperatively to 3.2° at the final visit, however, both had no statistical differences. Of the 40 levels underwent non-fusion procedure, 9 levels showed disc rehydration with 7 patients from Grade 4 to Grade 3 and 2 patients from Grade 3 to Grade 2. The other 30 cases did not show distinctive change. No screw loosening or rods breakage were detected during the follow-up periods. Conclusion: PEEK rods have obvious protective effects on degenerated intervertebral disc of non-fusion segments and the incidence of complications related to internal fixation is low. PEEK rods pedicle screw system is safe and effective in the treatment of lumbar degenerative diseases.
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Background: Skull osteosarcoma is relatively rare, and it is difficult to be diagnosed according to medical history and imaging examination due to the complex structure and diverse components of the brain. Consequently, there is only a limited number of patients who can undergo neoadjuvant chemotherapy before the operation. Although neoadjuvant chemotherapy plays an important role in the treatment of osteosarcoma, there is still a "bottleneck" in the current treatment method which when pulmonary metastasis occurs, or surgical treatment is not Enneking appropriate. Under such circumstances, the choice of treatment can be an issue. Case: A 16-year-old male patient with multiple metastases of skull osteosarcoma was reported. The patient suffered not only tinnitus and hearing loss in the right ear but also right facial paralysis and headache. The preoperative brain MRI showed a tumor in the right cerebellopontine angle (CPA) area. He underwent skull tumor resection at another hospital in November 2018, during which process the biopsy revealed epithelioid osteoblastoma-like osteosarcoma. The patient had supplemental radiotherapy 1 month after surgery because of tumor recurrence. 32 months afterward, pulmonary metastases and multiple bone metastases were found. Then the patient underwent multiple conservative treatments which include Denosumab, Anlotinib, and DIA (cisplatin + ifosfamide + doxorubicin) chemotherapy at our hospital. After a series of 6 cycles of treatment, the patient can walk without aid. Lactate dehydrogenase (LDH) and Alkaline phosphatase (AKP) returned to a normal level. Fluorodeoxyglucose (FDG) metabolism in all bone metastases decreased to normal except for the ones in the proximal left femur, and the FDG metabolism in the left femur is significantly lower than that before treatment. Multiple bone metastases showed different extents of high-density calcification, and the volume of the local bone metastases has been reduced significantly. The patient's condition stayed stable at latest follow-up. Conclusion: We found that multiple conservative treatments, which include Denosumab, Anlotinib and DIA chemotherapy, can improve patients' life quality, and help avoid further osteolytic destruction for patients with skull osteosarcoma and multiple metastases. Its specific mechanism and scope of the application still need to be further studied.
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BACKGROUND: Surgical treatment for recurrent bone tumors in the extremities still presents a challenge. This study was designed to evaluate the clinical value of microwave ablation in the treatment of recurrent bone tumors. METHODS: We present 15 patients who underwent microwave ablation for recurrent bone tumors during the last 7 years. The following parameters were analyzed for outcome evaluation: general condition, surgical complications, local disease control, overall survival, and functional score measured using the Musculoskeletal Tumor Society (MSTS) 93 scoring system. RESULTS: Percutaneous microwave ablation in one patient with osteoid osteoma and another with bone metastasis resulted in postoperative pain relief. Thirteen patients received intraoperative microwave ablation before curettage or resection, including those with giant cell tumors of bone (6), chondroblastoma (2), osteosarcoma (2), undifferentiated sarcoma (1), and bone metastases (2). All patients achieved reasonable local tumor control in the mean follow-up of 29.9 months. The functional score was 24.1 for the 15 patients 6 months after the operation. Four patients had tumor metastasis and died, whereas 3 patients with tumors survived, and the remaining 8 patients without the disease survived. CONCLUSIONS: Microwave ablation represents an optional method for local control in treating recurrent bone tumors in the extremities.
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Neoplasias Ósseas , Micro-Ondas , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Ósseas/patologia , Extremidades/patologiaRESUMO
BACKGROUND: Fast track surgery has shown its effectiveness to accelerate recovery and gained acceptance in many operations. However, data for paramedics using fast track surgery are limited in China. The aims of our study are to evaluate the knowledge, attitude and application status of fast track surgery in paramedics and to provide suggestions for the better application of fast track surgery. METHODS: Two Hundred Ninety-one operating room paramedics were investigated by simple random sampling from October 20 to December 20, 2019 time. A self-reported questionnaire was used to collect data with five dimensions: demographic data, cognitive level, knowledge, attitude and application of fast track surgery. Data were analyzed using qualitative and quantitative methods. RESULTS: 19.93% of participants never heard fast track surgery and only 3.32% of participants were very familiar with it. Gender (0.702, 95% CI 0.109-1.294), technical title (0.342, 95% CI 0.126-0.558) and awareness of the concept of fast track surgery (0.471, 95% CI 0.165-0.776) had a correlation with the knowledge level of paramedics towards fast track surgery. In terms of attitude towards fast track surgery, gender (- 1.944, 95% CI -3.830- -0.058), age (0.303, 95% CI 0.021-0.585) and knowledge score of fast track surgery (0.426, 95% CI 0.014-0.838) are related. Half of the paramedics believe the most difficult problem in the application of fast track surgery was the lack of multi-team communication and cooperation. CONCLUSION: The knowledge of fast track surgery among paramedics in Wuhan is poor, and some paramedics have a negative attitude towards it. As the attitude is positively correlated with the knowledge, it is necessary to improve the knowledge level of fast track surgery among paramedics in Wuhan.
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Conhecimentos, Atitudes e Prática em Saúde , Salas Cirúrgicas , Humanos , Estudos Transversais , Pessoal Técnico de Saúde , Inquéritos e QuestionáriosRESUMO
Background: Minimally invasive or open surgery is contentious in the treatment of spondylodiscitis, therefore finding a balance between the two is urgently needed. In this study, we propose a new treatment paradigm for treating spontaneous lumbar spondylodiscitis by percutaneous endoscopic lumbar debridement and irrigation drainage (PELDID). Then, the Pola classification was used to guide subsequent treatment. Methods: From November 2017 to April 2019, this study collected data on 16 patients with lumbar spondylodiscitis who were surgically treated utilizing this treatment paradigm in our department. Clinical effectiveness was determined using the visual analogue scale (VAS), the Oswestry Disability Index (ODI), the MOS 36-item short-form health survey (SF-36), and Kirkaldy-Willis criteria. Results: All 16 patients completed the treatment using the above paradigm and were followed up for 28.13 ± 10.15 months. The preoperative Pola classification is as follows: 7 cases of type A, 3 cases of type B, and 6 cases of type C. After the first-stage surgery, the evaluation results of Pola classification were as follows: 8 cases of type A, 8 cases of type B, and 0 cases of type C. Four patients received second-stage surgery with internal fixation through the paravertebral multifidus space approach and intervertebral bone graft fusion through the transforaminal approach, and the reoperation rate was 25% (4/16 cases). The Visual analogue scale (VAS), Oswestry Disability Index (ODI), and SF-36 score all improved significantly from 2.43 ± 0.89 to 0.18 ± 0.40, from 77.31% ± 11.15%to 16.93% ± 5.45%, and from 18.34 ± 7.47 to 80.3 ± 15.36. The CRP and ESR decreased dramatically from 49.61 ± 48.84 to12.50 ± 12.18 and from 65.56 ± 26.89 to 29.68 ± 20.68. There were no recurrences of infection in our study. Conclusions: The paradigm of the first-stage PELDID technique combined with the Pola classification system to guide the second-stage treatment for spontaneous spondylodiscitis is a novel and effective strategy for treating spontaneous spondylodiscitis.
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Discite , Fusão Vertebral , Humanos , Discite/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Desbridamento/métodos , Vértebras Lombares/cirurgia , Resultado do TratamentoRESUMO
1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is the primary molecular metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), a pesticide used to control the spread of dengue and Zika viruses, and can be detected in the majority of human blood samples. However, whether p,p'-DDE affects embryonic cardiac development remains unknown. This study aimed to explore the cardiotoxicity of p,p'-DDE and its potential mechanisms of action in zebrafish embryos. We demonstrated for the first time that zebrafish embryos exposed to p,p'-DDE exhibited cardiac development abnormalities, including morphological and functional abnormalities, such as pericardial edema, thinning of the ventricular wall, reduced erythrocyte intensity, and increased heart rate. The results of Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes and qRT-PCR showed that JAK-STAT-related genes (il17d, socs3a, and bcl2b) and Notch-related genes (notch1a, notch1b, bmp10, efnb2a, tbx2b, and tbx5a) were altered after p,p'-DDE treatment, leading to reduced proliferation and increased apoptosis of cardiomyocytes and irregular formation of ventricular and abnormal atrioventricular junctions. These results were verified using acridine orange staining, 5-ethynyl-2'-deoxyuridine assays, and whole-mount in situ hybridization. Our research suggests that p,p'-DDE affects cardiac development in zebrafish embryos and that its cardiotoxicity may be associated with the JAK-STAT and Notch signaling pathways. Our findings may provide the basis for future population-based cohort studies.
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Cardiotoxicidade , Diclorodifenil Dicloroetileno , Transdução de Sinais , Animais , DDT/toxicidade , Diclorodifenil Dicloroetileno/toxicidade , Peixe-Zebra/metabolismoRESUMO
PURPOSE: To evaluate the efficacy and safety of negative pressure wound therapy (NPWT) for post-operative deep surgical site infection (SSI) after posterior instrumented spinal surgery. METHODS: We retrospectively compared the clinical outcomes of NPWT with standard debridement for deep SSI after posterior instrumented spinal surgery from 2012 to 2020 in our department. The primary outcomes were peri-operative characteristics including positive organism results, duration of fever, and visual analogue scale (VAS) pain scores three days after re-operation. The secondary outcomes were post-operative characteristics including implant infection recurrence, implant retention rate, duration of hospitalization, and VAS at discharge. Pearson's chi-squared analysis (categorical) and Student's t test (continuous) were used to determine the differences. RESULTS: Thirty-four patients were included, of which 19 underwent NPWT, and 15 underwent standard debridement. Patients in the NPWT group all significantly improved primary outcomes including duration of fever after re-operation (0.95 ± 1.13 vs 4.07 ± 5.35, P = 0.001), positive organism results (14 of 19 vs 2 of 15, P < 0.01), and VAS at 3 days after re-operation (2.58 ± 0.69 vs 3.40 ± 1.06, P < 0.05). Patients in NPWT group exhibited significant decrease in implant infection recurrence (0 of 19 vs 5 of 15, P < 0.01), implant retention rate (19 of 19 vs 10 of 15, P < 0.01), duration of hospitalization (27.74 ± 10.95 vs 37.67 ± 13.67, P < 0.01). CONCLUSIONS: NPWT is a feasible and safe treatment option for deep SSI after posterior instrumented spinal surgery.
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Tratamento de Ferimentos com Pressão Negativa , Humanos , Região Lombossacral , Tratamento de Ferimentos com Pressão Negativa/métodos , Reoperação , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/terapiaRESUMO
INTRODUCTION: Head and neck squamous cell carcinomas (HNSCCs) are cancers with generally poor prognosis. Outcomes have not improved in decades, with more than half of the patients presenting with lymph node metastases at the time of diagnosis. A unique subtype of HNSCC, cancer of unknown primary of the head and neck (HNCUP) is associated with a poor outcome. Increased expression of the D2-40 gene (podoplanin) has been described for several human malignancies and has been associated with increased metastatic potential of cancer cells. METHODS: In order to examine the role of podoplanin in lymph node metastasis of HNSCC generally and HNCUP specifically, we evaluated the prognostic impact of podoplanin expression in HNSCC- (n = 68) and HNCUP-associated lymph node metastases (n = 30). The expression of podoplanin was analyzed by immunohistochemical staining of lymph node tissue samples and correlated with clinical and histopathological data. RESULTS: We found a non-significant tendency towards a higher podoplanin expression in HNCUP compared to HNSCC lymph node metastases and a significant correlation between a high podoplanin expression and advanced node-stage classification. Podoplanin expression had no significant impact on overall survival for both groups and did not correlate with human papillomavirus tumor status. CONCLUSION: Taken together, our results suggest that upregulation of podoplanin may be associated with a stimulation of lymphatic metastasis in head and neck cancer.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Primárias Desconhecidas , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Defects in pathways governing genomic fidelity have been linked to improved response to immune checkpoint blockade therapy (ICB). Pathogenic POLE/POLD1 mutations can cause hypermutation, yet how diverse mutations in POLE/POLD1 influence antitumor immunity following ICB is unclear. Here, we comprehensively determined the effect of POLE/POLD1 mutations in ICB and elucidated the mechanistic impact of these mutations on tumor immunity. Murine syngeneic tumors harboring Pole/Pold1 functional mutations displayed enhanced antitumor immunity and were sensitive to ICB. Patients with POLE/POLD1 mutated tumors harboring telltale mutational signatures respond better to ICB than patients harboring wild-type or signature-negative tumors. A mutant POLE/D1 function-associated signature-based model outperformed several traditional approaches for identifying POLE/POLD1 mutated patients that benefit from ICB. Strikingly, the spectrum of mutational signatures correlates with the biochemical features of neoantigens. Alterations that cause POLE/POLD1 function-associated signatures generate T cell receptor (TCR)-contact residues with increased hydrophobicity, potentially facilitating T cell recognition. Altogether, the functional landscapes of POLE/POLD1 mutations shape immunotherapy efficacy.
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DNA Polimerase II/genética , Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose/genética , Animais , DNA Polimerase III/genética , Humanos , Imunoterapia , Camundongos , Mutação , Neoplasias/genéticaRESUMO
Gestational diabetes mellitus (GDM) has become a global concern for its severe adverse effects on both mother and fetus. Recent epidemiological studies reported inconsistent results of the association between cadmium (Cd) exposure and GDM. Therefore, a systematic review and meta- analysis were performed. PubMed, Web of Science, Scopus, Embase, and SpringerLink were searched up to July 2021. Observational studies containing the adjusted relative risks between Cd exposure and GDM were included in the quantitative synthesis. The retrieval comprised 218 articles out of which 11 met our criteria and 9 were included in the meta-analysis, representing a total of 32,392 subjects (2881 GDM). In total, Cd exposure might increase the risk of GDM in some extent (OR = 1.21, 95% CI [0.89, 1.64]), even without statistical significance in high heterogeneity (Q = 28.45, p < 0.05, I2 = 71.9%). Filtering two outliers indicated by Galbraith plot yielded a similar risk (OR = 1.19, 95% CI [1.02, 1.39]) with statistical significance. However, the heterogeneity among studies was obviously reduced (Q = 11.75, p = 0.068, I2 = 48.9%). Additionally, biological specimen, study design, and diagnostic criteria contributed to the high heterogeneity according to the subgroup analysis. Since some important results do not deny that Cd exposure increases the risk of GDM, high-quality multi-centered large cohort studies are required in the future.
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Diabetes Gestacional , Gravidez , Feminino , Humanos , Cádmio/toxicidade , Estudos de CoortesRESUMO
Smart surfaces with switchable wettability are widely studied for environmental application. Although a large number of stimulation routes provide broad prospects for the development of smart surfaces, achieving high sensitivity, fast response and recovery, simple operation, security and good stability is still challenging. Herein, a Janus membrane via electrospinning, chemical bath deposition and heat treatment is constructed. By using the hydrophilic ZIF-L nanosheet to functionalize the hydrophobic thermoplastic polyurethane (TPU) substrate, a smart surface utilizes the ZIF-L crack induced by strain in the hydrophilic layer to control surface wettability is obtained. In the range of 0%-100% strain, the wettability of the smart surface presents an obvious change with stretching, and water contact angle of the surface shows a monotonic increase with a maximum tuning range from 47° to 114°. Due to local fusion of the TPU microfibers and good binding between the ZIF-L layer and the TPU substrate after heat treatment, the prepared Janus membrane exhibits consistent and symmetrical hydrophilic-hydrophobic-hydrophilic transition curves in 50 stretching-releasing cycles. Thanks to the porous and asymmetric architecture, the membrane shows good oil-water separation performance, and the separation flux increases with the increase of strain, while the separation efficiency is always higher than 98%. Because of the excellent structural stability, the robust membrane with 100% strain maintains its oil-water separation property for 50 stretching-releasing cycles. This study provides a new perspective for the development of smart material with stimuli responsive surface for oily wastewater purification.
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BACKGROUND: Limb salvage surgery for calcaneal sarcomas remains challenging due to its poor compartmentalization. While below-knee amputation is still the standard choice of operative treatment, total calcanectomy with or without reconstruction was advocated. This report aims to analyze the clinical outcome of calcaneal reconstruction with cement and replantation in situ after the inactivation of tumor. METHODS: We describe a 73-year-old male patient who suffered chronic pain and increasingly larger neoplasm in the left foot for about 3 years. Based on the results of percutaneous biopsy, a diagnosis of chondrosarcoma was made. RESULTS: The patient underwent total calcanectomy, inactivation of calcaneus tumor, and reconstruction with cement. The Achilles tendon was detached through a Cincinnati incision. No adverse events occurred both during and after the surgery. At the last follow-up of 29 months, the patient claimed no pain, no evident limp, or any limitation of daily activities. Image examination, weight-bearing test, and MSTS score revealed a satisfactory result. CONCLUSION: Calcaneal reconstruction with bone cement after total calcanectomy, inactivation of calcaneus tumor, and replantation in situ is likely to provide a feasible surgical choice and a satisfactory clinical outcome.
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Neoplasias Ósseas , Calcâneo , Condrossarcoma , Sarcoma , Masculino , Humanos , Idoso , Salvamento de Membro , Calcâneo/cirurgia , Calcâneo/patologia , Sarcoma/patologia , Condrossarcoma/cirurgia , Condrossarcoma/patologia , Extremidade Inferior/cirurgia , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/patologia , Resultado do TratamentoRESUMO
Plants have developed sophisticated mechanisms to survive in dynamic environments. Plants can communicate via volatile organic compounds (VOCs) to warn neighboring plants of threats. In most cases, VOCs act as positive regulators of plant defense. However, the communication and role of volatiles in response to drought stress are poorly understood. Here, we showed that tea plants release numerous VOCs. Among them, methyl salicylate (MeSA), benzyl alcohol, and phenethyl alcohol markedly increased under drought stress. Interestingly, further experiments revealed that drought-induced MeSA lowered the abscisic acid (ABA) content in neighboring plants by reducing 9-cis-epoxycarotenoid dioxygenase (NCED) gene expression, resulting in inhibition of stomatal closure and ultimately decreasing early drought tolerance in neighboring plants. Exogenous application of ABA reduced the wilting of tea plants caused by MeSA exposure. Exposure of Nicotiana benthamiana to MeSA also led to severe wilting, indicating that the ability of drought-induced MeSA to reduce early drought tolerance in neighboring plants may be conserved in other plant species. Taken together, these results provide evidence that drought-induced volatiles can reduce early drought tolerance in neighboring plants and lay a novel theoretical foundation for optimizing plant density and spacing.
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Telomerase reverse transcriptase (TERT) promoter mutations are prognostic in many cancers and have been observed in human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). However, the role of TERT promoter mutations in HPV-negative HNSCCs remains poorly understood in these cancers, which have increased risk for locoregional failure (LRF). PATIENTS AND METHODS: We retrospectively identified patients who were diagnosed with HNSCC between July 1, 2004, and October 12, 2017, at Memorial Sloan Kettering Cancer Center and whose tumors underwent next-generation sequencing using the MSK-IMPACT panel. Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) were excluded. Cumulative incidence of LRF, patterns of failure, and overall survival were measured. RESULTS: We identified 117 patients with SCC of the oral cavity (OSCC), larynx, hypopharynx, or HPV-negative oropharynx whose tumors underwent next-generation sequencing. Sequencing was performed on 95 tumors that were obtained after recurrence and 22 that were obtained before recurrence. TERT promoter mutations were enriched in OSCC compared with laryngopharyngeal cancers (81.1% v 7.0%; P < .001), which was the largest genetic difference between these anatomic disease subsites. TERT promoter mutations were associated with LRF in OSCCs (Gray's test, P < .001) and in the overall cohort (Gray's test, P < .001). On multivariate analysis, TERT promoter mutations were associated with an increased risk for LRF (subdistribution hazard ratio, 2.82; 95% CI, 1.47 to 5.42; P = .0019), independent of oral cavity primary site and TP53 mutation status. CONCLUSION: TERT promoter status is associated with the cumulative incidence of LRF and patterns of failure. TERT promoter mutations may define a subset of OSCCs with unique pathogenesis that is associated with an increased risk of LRF. Validation in prospective cohorts is warranted.