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BACKGROUND: The association between recurrence timing and prognosis in patients with locally advanced resectable esophageal cancer undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy remains unclear. This study aimed to clarify this association using multicenter prospective clinical trial data. METHODS: Among 162 patients enrolled in a NAC phase II study comparing the efficacy of cisplatin and fluorouracil plus docetaxel with cisplatin and fluorouracil plus adriamycin, 64 patients with recurrence after R0 resection were included in this study. We evaluated the association between recurrence timing and overall survival after recurrence (OSr), along with clinicopathological factors associated with recurrence timing and OSr. RESULTS: Among 64 patients, 46 (71.9%) and 59 (92.2%) experienced recurrence within 1 and 2 years after surgery, respectively. Groups based on recurrence timing, including ≤ 6, 6-12, and > 12 months, had median OSr of 3.6, 13.9, and 13.4 months, respectively. The prognosis was significantly poorer for patients with recurrence ≤ 6 months after surgery than for other patients (P < 0.001). Multivariate analysis revealed pathological lymph node staging as an independent factor associated with early recurrence (odds ratio: 3.46, 95% confidence interval: 1.47-8.02, P = 0.0045). On the other hand, multivariate analysis for factors associated with OSr revealed pT (hazard ratio [HR]: 1.91, 95%CI 1.26-2.88, P = 0.0022), early recurrence (HR: 6.88, 95%CI 2.68-17.6, P < 0.001), and treatment after recurrence, with both local treatment (HR: 0.47, 95%CI 0.22-0.98, P = 0.043) and chemotherapy (HR: 0.25, 95%CI 0.11-0.58, P = 0.0011) as independent prognostic factors. CONCLUSION: Patients with advanced esophageal cancer experiencing recurrence within 6 months after esophagectomy following NAC have an extremely poor prognosis, suggesting that an advanced pN stage is associated with early recurrence.
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Neoadjuvant therapy with nivolumab improves event-free survival (EFS) in patients with resectable non-small cell lung cancer, and a pathological complete response is a predictor of longer EFS. We assessed metabolic responses using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) before and after neoadjuvant treatment to explore its surrogacy for pathological complete response (pCR). We describe three patients with squamous cell lung carcinoma who underwent neoadjuvant therapy with nivolumab plus chemotherapy, followed by surgery. In Cases 1 and 2, preoperative tumour response were PR per RECIST and demonstrated marked metabolic response on FDG-PET after neoadjuvant therapy, with both resected tumours showing a pCR. On the other hand, Case 3 showed a tumour response before surgery (PR per RECIST), however, the tumour, maintained FDG uptake (19.5 â 15.1), and the resected tumour remained residual cells (RVT, 15%). Thus, reduction of FDG uptake on FDG-PET can predict the pathological response to neoadjuvant therapy with nivolumab.
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Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML-DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML-DS in Japan. Forty-eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine-related death was observed. One cycle concurrently administered with methotrexate-based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non-remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML-DS cases.
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Antimetabolitos Antineoplásicos , Azacitidina , Síndrome de Down , Leucemia Mieloide , Humanos , Síndrome de Down/complicaciones , Síndrome de Down/tratamiento farmacológico , Azacitidina/uso terapéutico , Azacitidina/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Antimetabolitos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/efectos adversos , Japón/epidemiología , Preescolar , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/complicaciones , Niño , Adolescente , Lactante , AdultoRESUMEN
Inhaled nitric oxide( iNO) therapy is commonly used to improve pulmonary hypertension and oxygenation in adult patients undergoing open heart surgery, mostly being applied to mechanical ventilation (MV). We often face rebound of pulmonary artery pressure (PAP) after reduction or discontinuation of iNO therapy, resulting in prolonged MV. Twenty-three cases, to which iNO therapy during MV (MV-iNO) were initiated, then continuously treated with iNO therapy using high-flow nasal cannula (HFNC-iNO) after extubation, were retrospectively investigated. During MV-iNO, mean PAP( mPAP) was significantly lower than before starting iNO therapy (p<0.001). Also, mPAP on HFNC-iNO was significantly lower than mPAP before iNO therapy during MV (p<0.001). There was no significant difference of mPAP between MV-iNO and HFNC-iNO (p=0.38). MV was discontinued in 330 minutes (median), oxygenation was maintained after switching from MV-iNO to HFNC-iNO and there were no cases of reintubation, perioperative mortality, or adverse events due to iNO therapy. HFNC-iNO is considered as useful method in maintaining decreased mPAP and improved oxygenation after extubation in adult patients after open heart surgery.
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Cánula , Procedimientos Quirúrgicos Cardíacos , Óxido Nítrico , Humanos , Masculino , Femenino , Óxido Nítrico/administración & dosificación , Anciano , Administración por Inhalación , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/cirugía , Anciano de 80 o más Años , Respiración ArtificialRESUMEN
Steric manipulation is a known concept in molecular recognition but there is currently no linear free energy relationship correlating sterics to the stability of receptor-anion complexes nor to the reactivity of the bound anion. By analogy to Tolman cone angles in cation coordination chemistry, we explore how to define and correlate cone angles of organo-trifluoroborates (R-BF3 -) to the affinities observed for cyanostar-anion binding. We extend the analogy to a rare investigation of the anion's reactivity and how it changes upon binding. The substituent on the anion is used to define the cone angle, θ. A series of 10â anions were studied including versions with ethynyl, ethylene, and ethyl substituents to tune steric bulk across the sp, sp2 and sp3 hybridized α-carbons bearing 0, 1 and 2â hydrogen atoms. A linear relationship between affinity and cone angle is observed for anions bearing substituents larger than the -BF3 - headgroup. This correlation predicted affinities of two new anions to within ±5 %. We explored how complexation affects the reactivity of fluoride exchange. The yield of fluoride transfer from R-BF3 - to Lewis acid triphenylborane is correlated with cone angle. We predict that other rigid macrocycles, like commercially available bambusuril, could follow these trends.
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OBJECTIVES: Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis. MATERIALS AND METHODS: This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities. RESULTS: Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9-17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88-0.91), 0.85 (0.84-0.87), 0.83 (0.81-0.85), and 0.85 (0.82-0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84-0.92), 0.84 (0.78-0.88), 0.84 (0.76-0.89), and 0.84 (0.75-0.90) at 180, 360, 720, and 1,080 days, respectively. CONCLUSION: This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings.
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Neoplasias Pulmonares , Aprendizaje Automático , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Masculino , Femenino , Anciano , Pronóstico , Estudios Retrospectivos , Persona de Mediana Edad , Estadificación de Neoplasias , Algoritmos , Curva ROC , Anciano de 80 o más Años , Estudios de CohortesRESUMEN
BACKGROUND AND OBJECTIVE: Acute exacerbation of fibrosing interstitial lung disease (AE-FILD) is a serious condition with a high mortality rate. We aimed to comprehensively analyze cytokines in bronchoalveolar lavage fluid and their association with the clinical course of AE-FILD. METHODS: We retrospectively enrolled 60 patients with AE-FILD who underwent bronchoalveolar lavage. We comprehensively measured 44 cytokines and chemokines in the obtained bronchoalveolar lavage fluid using a Luminex analyzer. Patients were grouped into those who died within 90 days (non-survival group) and survived beyond 90 days (survival group) to investigate the association of the levels of cytokines and chemokines with mortality. RESULTS: The levels of matrix metalloproteinase 1 (p = 0.003), granulocyte-macrophage colony-stimulating factor (p = 0.040), interleukin 6 (p = 0.047), interleukin 8 (p = 0.050), monocyte chemoattractant protein-1 (p = 0.043), and eotaxin (p = 0.044) were significantly higher in the non-survival group than in the survival group. In the receiver operating characteristic analysis, their areas under the curve were 0.80, 0.68, 0.71, 0.70, 0.70, and 0.72, respectively. Using machine learning with these six cytokines and chemokines, the predictive accuracy for the survival group was 0.94. CONCLUSIONS: Our study demonstrated that several cytokines and chemokines in bronchoalveolar lavage fluid could be prognostic predictors in patients with AE-FILD.
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Líquido del Lavado Bronquioalveolar , Quimiocinas , Citocinas , Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales , Humanos , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Femenino , Masculino , Pronóstico , Citocinas/metabolismo , Anciano , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/metabolismo , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/diagnóstico , Quimiocinas/metabolismo , Quimiocinas/análisis , Persona de Mediana Edad , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/análisis , Interleucina-6/metabolismo , Interleucina-6/análisis , Interleucina-8/metabolismo , Interleucina-8/análisis , Quimiocina CCL11/metabolismo , Quimiocina CCL11/análisis , Biomarcadores/metabolismo , Biomarcadores/análisisRESUMEN
The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy.
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Prognostic stratification is an urgent concern for patients with colorectal cancer (CRC). The desmoplastic reaction (DR) is speculated to mirror the tumor microenvironment. DR types are considered independent prognostic indicators in CRC, but have not been incorporated in previous prognostic nomograms. We aimed to assess the prognostic significance of a novel approach incorporating histopathological indicators reflecting tumor glandular differentiation and microenvironment. We evaluated 329 consecutive patients with CRC who underwent surgical resection at Kansai Medical University. Histological glandular differentiation was scored as 2 (0 point), 3 (1 point), or 4 (2 points). Tumor buddings (TBs) were classified as TB1 (0 point), TB2 (1 point), or TB3 (2 points). pT1 or 2 was considered as 0 point, pT3 or 4 + DR non-immature type as 1 point, and pT3 or 4 + DR immature type as 2 points. Lymph node metastasis was classified as pN0 (0 point), pN1 (1 point), or pN2 (2 points). The preoperative carcinoembryonic antigen levels were categorized as < 5.0 ng/mL (0 point) and â§5.0 (1 point). Considering these factors, the following D&M (tumor differentiation and microenvironment) scoring system was applied: I (0-2 points), II (3-4 points), III (5-6 points), and IV (7-9 points). Kaplan-Meier curves showed significant differences in disease-specific survival and recurrence-free survival among the assigned scores, highlighting their enhanced utility compared with the American Joint Committee on Cancer 8th edition staging system. The D&M scoring system was valuable as the initial prognostic nomogram, including DR.
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Neoplasias Colorrectales , Microambiente Tumoral , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Femenino , Masculino , Anciano , Pronóstico , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Diferenciación Celular , Estadificación de Neoplasias , Metástasis Linfática , NomogramasRESUMEN
Background: We have proposed the concept of glenoid track ("on-track/off-track" lesion) to evaluate the risk of engagement of the Hill-Sachs lesion with the glenoid after arthroscopic Bankart repair. This concept has been widely used and many clinical validation studies have been reported. To measure the glenoid track width, we have recommended to use 3-dimensional computed tomography (CT) images. However, the CT method has the issue of radiation exposure and involves time and effort to make 3-dimensional CT images from 2-dimensional images. For these reasons, there are several reports describing the measurement method using magnetic resonance imaging. Recently, the threshold of the critical glenoid bone loss becomes lower. A zone of bone loss below the critical size is called "subcritical bone loss", which might be related to deterioration of quality of life and bone grafting is recommended. We applied the concept of "subcritical bone loss" to the glenoid track. Patients with "on-track" lesions can be divided into 2 subgroups: those with a "peripheral-track" lesion (most medial 1/4) and those with a "central-track" lesion (the rest 3/4). More recently, similar evaluation methods to evaluate the risk of "off-track" lesions have been reported: ''distance to dislocation'' and "Hill-Sachs interval/glenoid track ratio". Also, similar concept to "peripheral-track" lesion, "near-track" lesion was reported. The concept of "peripheral-track" lesion is a concept of assessing an "on-track" lesion which is very close to the medial margin of the glenoid track (subcritical bone loss). Methods: Similar evaluation methods to evaluate the risk of "off-track" or "peripheral-track" lesions were proposed in the literature. A review was performed by searching PubMed. Journal articles published between January 2014 and January 2023 were taken into account. They were compared and their differences were explained. Results: The "near-track" lesion concept is similar to "peripheral-track" lesion. However, the cutoff value is different: Hill-Sachs occupancy ≥ 75% is the "peripheral-track" lesion, whereas "distance to dislocation" < 8 mm is the "near-track" lesion. Conclusion: We introduced update of the glenoid track concept including the evaluation method, peripheral-track lesion, and its clinical application.
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Background: Recurrence rates after first-time shoulder dislocation in young patients are high, especially in their early teens. Only a few studies have arthroscopically investigated the inside of the glenohumeral joint in young patients. Such arthroscopic investigation would help in solving the cause of the greater incidence of recurrent instability in the young population, especially in their early teens. Methods: Data from 42 patients with first-time anterior shoulder dislocation were retrospectively reviewed. The participants were divided into two groups: those aged 10 to 15 years at the time of the dislocation (adolescent group) and those aged 20- 29 years (adult group). The arthroscopic findings regarding the glenohumeral joint in the adolescent group were assessed and compared to those in the adult group. The intra-articular pathology was examined in all cases and recorded with specific reference to (1) the anterior capsulolabral lesion, (2) Hill-Sachs lesion, (3) labrum-anteroinferior glenohumeral ligament complex, and (4) other concomitant lesions. Results: Anterior joint laxity was found more in the adolescent group than in the adult group (P = .046). Thirty-six (83%) shoulders had Hill-Sachs lesions: 6 shoulders (60%) in the adolescent group and 30 shoulders (97%) in the adult group, with a significant difference (P < .001). Conclusion: Pathological findings observed during arthroscopy are more common in the adult group, whereas recurrent instability is more likely in adolescent group.
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BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.
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Antineoplásicos , Náusea , Neoplasias , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Náusea/inducido químicamente , Náusea/prevención & control , Neoplasias/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Vómito Precoz , Hipnosis , Yoga , Antieméticos/uso terapéuticoRESUMEN
BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.
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Antieméticos , Oncología Médica , Vómitos , Humanos , Japón , Oncología Médica/normas , Antieméticos/uso terapéutico , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Sociedades Médicas , Náusea/prevención & control , Náusea/tratamiento farmacológicoRESUMEN
Non-high-risk (non-HR) neuroblastoma (NB) patients have excellent outcomes, with more than a 90% survival rate, whereas HR NB patients expect less than a 50% survival rate. Metastatic disease is the principal cause of death among both non-HR and HR NB patients. Previous studies have reported the significant but limited prognostic value of quantitative PCR (qPCR)-based assays, measuring overlapping but different sets of neuroblastoma-associated mRNAs (NB-mRNAs), to detect metastatic disease in both non-HR and HR patient samples. A droplet digital PCR (ddPCR)-based assay measuring seven NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was recently developed and exhibited a better prognostic value for HR patient samples than qPCR-based assays. However, it remained to be tested on non-HR patient samples. In the present study, we employed the ddPCR-based assay to study peripheral blood (PB) and bone marrow (BM) samples collected at diagnosis from eight non-HR and eleven HR cases and characterized the expression profiles of NB-mRNAs. The most highly expressed NB-mRNAs in PB and BM differed between non-HR and HR cases, with the CRMP1 mRNA being predominant in non-HR cases and the GAP43 mRNA in HR cases. The levels of NB-mRNAs in PB and BM were 5 to 1000 times lower in non-HR cases than in HR cases. The PB to BM ratio of NB-mRNAs was 10 to 100 times higher in non-HR cases compared to HR cases. The present case series suggests that non-HR and HR NB patients have the distinct expression profiles of NB-mRNAs in their PB and BM.
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Prevalence of impaired foot function among baseball players with and without a disabled throwing shoulder/elbow was investigated. The study included 138 male players. Players who had previously complained of shoulder/elbow pain during throwing motion were defined as the players with a history, and those who experienced shoulder/elbow pain during the examination were defined as having the injury. Foot function was evaluated by foot "rock paper scissors" movements and floating toes. Their prevalence was assessed and the relationships between players with and without the injuries were statistically analyzed. The prevalence of players with a history and injury was 27% and 7%, respectively. The prevalence of impaired foot function on the non-throwing side among players with injury was significantly higher than those without (60% vs. 28%, P < 0.001) and higher tendency on the throwing side than those without (60% vs. 32%). Regarding floating toes, players with a relevant history showed a significantly higher prevalence on the throwing side than those without (49% vs 28%, P < 0.001) and higher tendency on the non-throwing side than those without (49% vs 32%). Players with disabled throwing shoulder/elbow have a significantly higher prevalence of impaired foot function and floating toes than players without it.
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Béisbol , Pie , Humanos , Masculino , Béisbol/lesiones , Estudios de Casos y Controles , Prevalencia , Pie/fisiopatología , Pie/fisiología , Adulto Joven , Adulto , Hombro/fisiopatología , Personas con DiscapacidadRESUMEN
The reaction of equimolar trimethylsilyldiazomethyllithium (LiTMSD) with high spin (S = 2) PhB(AdIm)3FeCl (PhB(AdIm)3- = tris(3-adamantylimidazol-2-ylidene)phenylborate) affords the corresponding N-nitrilimido complex PhB(AdIm)3Fe-NâNâC(SiMe3). This complex can be converted to the thermodynamically more favorable C-isocyanoamido isomer PhB(AdIm)3Fe-CâNâN(SiMe3) by reaction with an additional equivalent of LiTMSD. While the iron(II) complexes are four-coordinate, the diazomethane is bound side-on in the iron(I) congener PhB(AdIm)3Fe(N,N'-κ2-N2C(H)Si(CH3)3). The latter complex adopts high spin (S = 3/2) ground state and features an unusually weak C-H bond. Photolysis of the iron(II) complexes induces NâN bond cleavage, with the iron(II) cyanide PhB(AdIm)3Fe-C≡N and iron(IV) nitride PhB(AdIm)3Fe≡N complexes being the major products of the reaction. The same products are obtained when the iron(I) complex is photolyzed or treated with a fluoride source. The trimethylsilyldiazomethane-derived ligand disassembly reactions are contrasted with those observed for related tris(carbene)amine complexes.
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Antibody-drug conjugates (ADCs) have emerged as a novel class of anticancer treatment. ADCs are composed of three parts: a monoclonal antibody, a linker and a payload. A monoclonal antibody binds to the specific antigen present at the cancer cells, allowing selective delivery of the cytotoxic agents to the tumor site. Several ADCs are approved by the US Food and Drug Administration for the treatment of hematologic cancers and solid tumors with clinically meaningful survival benefit. However, the development of ADCs faces a lot of challenges and there is a need to get better understanding of ADCs in order to improve patient outcomes. Here, we briefly discuss the structure and mechanism of ADCs, as well as the clinical data of current approved ADCs in solid tumors.
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Inmunoconjugados , Neoplasias , Humanos , Inmunoconjugados/uso terapéutico , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
The risk of Hill-Sachs lesion (HSL) to cause instability depends not only on the HSL but also on the glenoid size. Clinically, the only method to assess the risk of instability considering the dynamic interaction of both, the HSL together with the glenoid bone loss, is the glenoid track concept. Since it was introduced in a cadaveric study, its clinical efficacy and validity have been reported in the literature. Sometimes, the medial margin of the footprint (lateral margin of the glenoid track) is difficult to identify when a HSL is overriding the footprint. In such cases, we propose a method to draw an imaginary line connecting 2 landmarks. Although 3-dimensional computed tomography is the most accurate and widely used method to assess on/off-track lesions, our interest gradually is shifting toward magnetic resonance imaging (MRI), which has no radiation concern. The current magnetic resonance method is still under way. There are various risk factors influencing the recurrent instability after surgery. The glenoid track concept deals with only 1 of these factors, that is, instability caused by bony lesions. Therefore, the following 2 issues are important: 1) how to assess the glenoid track precisely and 2) how to incorporate other risk factors into consideration. The former can be achieved by obtaining the custom-made glenoid track width using not the fixed value of 83%, but more individualized value obtained by measuring the active horizontal extension angle of the opposite shoulder in the sitting position. At the same time, the gray zone (peripheral-track lesion) needs to be clearly defined. The latter can be achieved by incorporating the risk factors other than the bony lesions. One example is the Glenoid Track Instability Management Score (GTIMS), a combination of the glenoid track concept and the instability severity index score. This new scoring system is expected to increase the predictive potential of the scoring system, and accordingly to enhance clinical decision-making.
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The standard treatment for resectable non-small cell lung cancer (NSCLC) located in the superior sulcus is neoadjuvant chemoradiotherapy followed by highly invasive resection. Based on the results of the CheckMate 816 trial, which showed a marked improvement in the efficacy of neoadjuvant chemo-immunotherapy, we report a case of minimally invasive resection after neoadjuvant nivolumab plus chemotherapy for superior sulcus NSCLC, resulting in a pathologic complete response. The patient was a 76-year-old man with a 65-mm right superior sulcus tumour diagnosed as squamous cell carcinoma with 95% PD-L1. After two courses of neoadjuvant nivolumab plus chemotherapy, the tumour was completely resected through an 11-cm right lateral thoracotomy with second rib resection and first rib preservation. No residual tumour cells were observed in the specimen, and the patient had a pathologic complete response. This report represents a new treatment option for superior sulcus tumours.