RESUMO
Aim: Tumor markers often remain elevated after intended curative resection of medullary thyroid carcinoma (MTC). The aim of this study was to determine the expression of αvß3, a promising theranostics target, in MTC and its metastases. Materials & methods: Avß3 expression was analyzed in 104 patients using a tissue microarray and correlated with clinicopathological variables and survival. Results: Cytoplasmic αvß3 positivity was seen in 70 patients and was associated with lymph node metastases at time of initial surgery. Membranous positivity was considered positive in 30 patients and was associated with sporadic MTC. Conclusion: Avß3 was expressed in the cytoplasm of 67% of MTC patients. Membranous expression, which is presumably most relevant for the theranostic use of αvß3, was seen in 29%.
[Box: see text].
RESUMO
BACKGROUND: Nasal valve dysfunction (NVD) is a substantial contributor to nasal airway obstruction. Minimally-invasive temp-erature-controlled radiofrequency (TCRF) treatment of the nasal valve is available and comparison with surgical techniques is warranted. METHODOLOGY: Databases: Medline (PubMed), Embase, Cochrane Library. POPULATION: adults with preprocedural nasal obstruction symptom evaluation (NOSE) score >=45. Treatment effects were derived from a random effects model and reported as weighted mean difference in NOSE score between baseline; 3, 6, and 12 months postprocedure. RESULTS: Of 2529 initial articles, 5 studies describing TCRF treatment and 63 studies describing functional rhinoplasty were included. Pooled effect sizes for TCRF treatment and functional rhinoplasty were comparable in all analyses. CONCLUSIONS: TCRF treatment of the internal nasal valve for NVD was associated with sustained effects comparable to functional rhinoplasty addressing the nasal valve only, rhinoplasty without concomitant turbinate treatment, and all rhinoplasty.
Assuntos
Obstrução Nasal , Rinoplastia , Humanos , Rinoplastia/métodos , Obstrução Nasal/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Temperature-controlled radiofrequency (TCRF) device treatment of nasal valve dysfunction (NVD) was superior to a sham procedure control in reducing the symptoms of nasal airway obstruction (NAO) in this randomised controlled trial (RCT). METHODOLOGY: Two-year outcomes for 108 patients actively treated in a prospective, multicenter, patient-blinded RCT were used to determine treatment effect durability and changes in medication/nasal dilator usage. A responder was defined as ≥ 20 reduction in NOSE score or 1 reduction in severity class. RESULTS: The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) women. Baseline NOSE score was 76.3. The 2-year responder rate was 90.4% and NOSE score treatment effect was -41.7; 54.7% improvement. Of 57 patients using medications/nasal dilators at baseline, 45 (78.9%) either stopped all use (33.3%) or stopped/decreased (45.6%) use in >=1 class at 2 years. Concurrent septal deviation, septal swell body, or turbinate enlargement did not significantly affect the odds of exhibiting a NOSE score of ≤ 25 at 2 years. CONCLUSIONS: TCRF device treatment of NVD resulted in significant and sustained improvements in the symptoms of NAO at 2 years, accompanied by a substantial reduction in medication/nasal dilator use.
Assuntos
Obstrução Nasal , Humanos , Obstrução Nasal/cirurgia , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Resultado do Tratamento , Adulto , Terapia por Radiofrequência/métodosRESUMO
BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.
Assuntos
Anticorpos Monoclonais Humanizados , Pólipos Nasais , Rinite , Sinusite , Humanos , Sinusite/tratamento farmacológico , Sinusite/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Doença Crônica , Rinite/tratamento farmacológico , Rinite/complicações , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/etiologia , Olfato/efeitos dos fármacos , Olfato/fisiologia , Método Duplo-Cego , Resultado do Tratamento , Teste de Desfecho Sinonasal , RinossinusiteRESUMO
BACKGROUND: This randomised, double-blind, placebo-controlled, parallel-group, 52-week Phase III study (MERIT; NCT04607005) assessed mepolizumab efficacy and safety in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS (ECRS) in Japan, Russia, and China, for which data are limited. METHODOLOGY: Eligible patients (enrolled at 60 centres) had blood eosinophil count >2%, endoscopic bilateral NP score ≥5, nasal obstruction visual analogue scale (VAS) score >5, ≥2 sinonasal symptoms, and either previous sinus surgery or systemic corticosteroid use/intolerance. Patients were randomised (1:1) to receive mepolizumab 100 mg subcutaneously or placebo every 4 weeks, plus standard of care. Co-primary endpoints: change from baseline in total endoscopic NP score (ENPS) (Week 52) and nasal obstruction VAS score (Weeks 49-52). Post hoc analyses conducted in a modified intent-to-treat (mITT) population excluded patients from two study sites, related to Good Clinical Practice violations by the Site Management Organisation overseeing these sites. These were considered the primary efficacy analyses. RESULTS: In the mITT population, mepolizumab (n=80) versus placebo (n=83) significantly improved nasal obstruction VAS score from baseline to Week 49-52 and was associated with a trend of total ENPS improvements at Week 52. Mepolizumab/placebo on-treatment adverse events (AEs) occurred in 68/84 and 65/85 patients in the safety population (treatment-related AEs: 2/84 and 5/85, respectively), and on-treatment serious AEs in 0/84 and 4/85 patients, respectively (no fatalities reported). CONCLUSIONS: Mepolizumab was effective and well-tolerated in patients with CRSwNP/ECRS from Japan, Russia, and China.
RESUMO
Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.
Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Sinusite/terapia , Rinite/terapia , Doença Crônica , Pólipos Nasais/terapia , Pólipos Nasais/complicações , Qualidade de VidaRESUMO
Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.
Assuntos
Atrofia , Cognição , Disfunção Cognitiva , Substância Cinzenta , Imageamento por Ressonância Magnética , Esclerose Múltipla , Humanos , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Estudos Transversais , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Disfunção Cognitiva/etiologia , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagem , Testes Neuropsicológicos , Masculino , FemininoRESUMO
Objective: To investigate the clinicopathological characteristics and genetic mutations of SMARCA4-deficient lung adenocarcinoma. Methods: From January 2021 to April 2023 in the First Affiliated Hospital of Zhengzhou University, 42 cases of SMARCA4-deficienct lung adenocarcinoma were diagnosed and now analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed. Next-generation sequencing (NGS) was performed to investigate the mutations of related genes. Results: Among the 42 cases, there were 35 biopsy and 7 surgical specimens. There were 38 males and 4 females. The male to female ratio was 9.5â¶1.0, with an age range from 42 to 78 years. Thirty-three patients were smokers. Overall, 4 cases (9.5%), 2 cases (4.7%), 18 cases (42.9%) and 18 cases (42.9%) were at stages â , â ¡, â ¢, and â £, respectively. Microscopically, all the cases were non-mucinous adenocarcinoma, without lepidic pattern. The morphology was diverse. Rhabdomyoid cells, tumor giant cells and tumor necrosis were present. Most of the tumor cells had eosinophilic cytoplasm and occasionally clear cytoplasm. Defined cell borders and variable cytoplasmic hyaline secretory globules could be found. Inflammatory cells infiltrated the tumor stroma. Immunohistochemistry showed 29 cases (69.0%, 29/42) expressed TTF1, 10 cases (40.0%, 10/25) expressed Napsin A, and 20 cases (100.0%, 20/20) expressed INI1. Forty cases (95.2%, 40/42) showed BRG1 loss in all tumor cells, while 2 cases (4.8%, 2/42) had partial BRG1 loss. PD-L1 (22C3) was positive in 59.2% of the cases (16/27). NGS revealed mutations in EGFR, ROS1, MET, RET and KRAS. Six cases (6/8) showed SMARCA4 mutation, while some cases were accompanied by mutations of TP53 (7/15), STK11 (4/8), and KEAP1 (1/8). Driver gene mutations were more common in women (P<0.05). Patients were followed up for 1-25 months. Four patients died and 20 patients' diseases progressed. Conclusions: SMARCA4-deficient lung adenocarcinoma lacks characteristic morphology. Most of them express TTF1 and harbor driver gene mutations. It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteínas Tirosina Quinases/genética , Estudos Retrospectivos , Proteínas Proto-Oncogênicas/genética , Fator 2 Relacionado a NF-E2/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Mutação , Biomarcadores Tumorais/genética , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genéticaRESUMO
Currently, obesity and its complications have become increasingly serious health issues. Bariatric surgery is an effective method of treating obesity and related metabolic complications. Among them, Roux-en-Y gastric bypass (RYGB) is still considered the "gold standard" procedure for bariatric surgery. Small bowel obstruction is one of the possible complications after RYGB, and in addition to the formation of intra-abdominal hernias, kinking of the jejunojejunal anastomosis is an important cause of small bowel obstruction. The early clinical symptoms of kinking of the jejunojejunal anastomosis often lack clarity in the early stages. Therefore, early diagnosis, prevention, and effective treatment of kinking of the jejunojejunal anastomosis are challenging but crucial. The occurrence of kinking of the jejunojejunal anastomosis may be related to surgical techniques and the surgeon's experience. The use of anti-obstruction stitch, mesenteric division, and bidirectional jejunojejunal anastomosis may be beneficial in preventing kinking of the jejunojejunal anastomosis. If kinking of the jejunojejunal anastomosis occurs, timely abdominal CT scans and endoscopic examinations should be performed. Gastric and intestinal decompression should be initiated immediately, and exploratory surgery should be prepared.
Assuntos
Derivação Gástrica , Obstrução Intestinal , Complicações Pós-Operatórias , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Derivação Gástrica/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Laparoscopia/métodos , Jejuno/cirurgia , Intestino Delgado/cirurgia , Anastomose em-Y de Roux/métodosRESUMO
Objective: To explore the impact of uncertain resection on postoperative survival in non-small cell lung cancer. Methods: This is a retrospective cohort study. A retrospective analysis was conducted on the data of 477 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2012 to December 2013. There were 302 males and 175 females, aged (59±8) years (range: 27 to 79 years). According to the surgical resection criteria issued by the International Association for the Study of Lung Cancer, the patients were divided into the intact resection group (R0 group, 286 cases) and the uncertain resection group (R (un) group, 191 cases). Clinical data between the two groups were compared using χ2 test, and propensity score matching (PSM) was performed on patients using the R language, with matching variables including gender, age, smoking history, adjuvant therapy, TNM stage, pathological type, and tumor site. The nearest-neighbor method was used for 1â¶3 matching and the caliper value was 0.02. The survival curve was plotted using the Kaplan-Meier method and compared using the Log-rank test. The Cox proportional hazards regression model was used to identify risk factors in overall survival (OS). Subgroup analysis was based on TNM staging and mediastinal lymph node metastasis status. Results: In the R (un) group, 68 patients had positive lymph in the highest group and 129 patients did not undergo complete dissection of the mediastinal lymph nodes. The baseline data for the R0 group and the R (un) group were corrected using PSM, and a total of 369 patients were successfully matched, including 227 cases in the R0 group and 142 cases in the R (un) group. After PSM, the 5-year survival rates of the R0 group and the R (un) group were 64.3% and 52.1%, respectively (P=0.021). The 5-year survival rates of stage â , â ¡, and â ¢ patients were 85.2%, 65.9%, and 34.8%, respectively (P<0.01). TNM stage (χ2=46.913, P<0.01), pathological classification of adenosquamous cell carcinoma (HR=5.970, 95% CI: 3.117 to 11.431, P<0.01) and R (un) resection (HR=1.512, 95% CI: 1.065 to 2.147, P=0.021) were prognostic factors for postoperative survival. Subgroup analysis showed that in stage â ¢ patients, 5-year survival rates of the R0 group and the R (un) group after resection were 45.8% and 9.5%, respectively (P=0.002). Among patients with mediastinal lymph node metastasis, 5-year survival rates of the R0 group and the R (un) group were 50.6% and 7.1%, respectively (P<0.01). Conclusions: TNM staging, pathological type, and R (un) resection are prognostic factors for overall postoperative survival in non-small cell lung cancer. In stage â and â ¡ patients, R (un) is not a prognostic factor for postoperative survival of non-small cell lung cancer. In patients with stage â ¢ and mediastinal lymph node metastasis, R (un) is a prognostic factor for non-small cell lung cancer after surgery.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Prognóstico , Adulto , Idoso , Pneumonectomia , Estadiamento de Neoplasias , Metástase Linfática , Taxa de Sobrevida , Pontuação de PropensãoRESUMO
BACKGROUND: Developmental dysplasia of the hip (DDH) is common in performing artists and other young active individuals and involves abnormalities in bony morphology of the acetabulum and proximal femur that can negatively impact walking biomechanics, muscular strength, quality of life, and sleep. Rehabilitation for hip-related conditions should target known modifiable impairments such as hip muscle strength, though a reliable method of assessment in this population remains unclear. OBJECTIVE: To determine the inter- and intra-rater reliability of hip muscle strength assessments using handheld dynamometry (HHD) in young active circus artists with DDH. METHODS: Reliability of hip strength in all planes was assessed using HHD in 21 adult performing circus arts students (mean age 21.3 yrs [3.2]; 13 M, 5 F, 3 NB) with symptomatic radiologically and clinically diagnosed hip dysplasia. The reliability of average peak force and absolute peak force were expressed for each position tested. Reliability was assessed using intraclass correlation coefficients (ICC) with standard error of measurement (SEM) and minimal detectable change (MDC) values calculated to improve clinical interpretability. RESULTS: Good to excellent inter-rater reliability resulted for all hip muscle strength testing positions, ICC=0.88 (95%CI 0.70 to 0.95) to ICC=0.97 (0.92 to 0.99), except average peak hip flexion strength, ICC=0.71 (0.28 to 0.88). Absolute peak hip abduction, ICC=0.77 (0.16 to 0.94), and adduction strength, ICC=0.72 (-0.55 to 0.92), demonstrated the lowest intra-rater reliability. Transverse plane strength measures (rotation) produced the lowest SEM and MDC values followed by the frontal plane (abduction/adduction) and sagittal plane (flexion/extension). CONCLUSION: HHD is an appropriate and reliable method to assess hip muscle strength in circus artists with DDH.
Assuntos
Força Muscular , Humanos , Força Muscular/fisiologia , Reprodutibilidade dos Testes , Feminino , Masculino , Adulto Jovem , Articulação do Quadril/fisiopatologia , Dinamômetro de Força Muscular , Adulto , Displasia do Desenvolvimento do Quadril/fisiopatologiaRESUMO
Objective: To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD). Methods: This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results: A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm2 vs. (47.9±23.8) cm2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group (P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group (P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition (P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score (r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score (r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95%CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95%CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95%CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95%CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence (OR=6.616, 95%CI: 1.383-31.656, P=0.018; OR=5.548, 95%CI: 1.062-28.973, P=0.042). Conclusion: Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.
Assuntos
Composição Corporal , Doença da Artéria Coronariana , Gordura Intra-Abdominal , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Estudos Transversais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Gordura Intra-Abdominal/diagnóstico por imagem , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/complicações , Calcificação Vascular/fisiopatologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.
Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Masculino , Humanos , Criança , Feminino , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos T CD8-PositivosRESUMO
Objective: To investigate the MRI imaging features of hepatocyte nuclear factor 1α- inactivated hepatocellular adenoma (H-HCA). Methods: Clinical data and MRI images of 19 H-HCA cases who were pathologically confirmed at Zhongshan Hospital Affiliated to Fudan University between August 2014 and July 2020 were retrospectively analyzed. Among them, there were 15 females and 4 males, aged 16-47 (32± 7) years old. Tumor number, location, shape, size, boundary, MRI plain scan signal intensity, dynamic enhancement features of each phase, presence or absence of intratumoral fat content, pseudocapsule, and others were analyzed. The differences in apparent diffusion coefficient (ADC) values between the lesion and the surrounding normal liver parenchyma were compared for statistical significance. t-test was used for statistical analysis. Results: There were a total of 24 lesions in 19 cases. 14 cases had solitary lesions, and five cases had multiple lesions. 15 and nine lesions were located in the right and left lobes of the liver, respectively. 20 lesions were round or quasi-round, and four were irregular or lobulated. The tumor's maximal diameter was 0.6-8.6 (3.5 ± 2.4) cm. T(1)-weighted image (WI) showed hyperintense to iso-intense signals in 20 lesions and hypointense signals in four. T(2)WI showed iso-to-slightly high signal intensity in 16 lesions, with two hyperintense and six hypointense signals. Diffusion-weighted image (DWI) revealed hyperintense to iso-intense signals. Lesions mean ADC value was (1.289 ± 0.222)×10(-3) mm(2)/s, while the adjacent normal liver parenchyma's mean ADC value was (1.307 ± 0.236)×10(-3) mm(2)/s, with no statistically significant difference between the two (P > 0.05). During the arterial phase, 15 of the 18 lesions that underwent dynamic contrast-enhanced scanning with gadoxetate disodium (Gd-DTPA) were mildly to moderately enhanced and three were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the delayed phase showed a hypointense signal. During the arterial phase, two of the six lesions scanned by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ((Gd-EOB-DTPA) dynamic enhancement were mildly to moderately enhanced, while four were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the transition and hepatobiliary-specific phases showed hypointense signals. Intracellular steatosis occurred in 21 lesions, of which 19 were diffuse steatosis and 16 formed pseudocapsules in the delayed phase. Conclusion: H-HCA often occurs in young females as solitary lesions and has certain MRI features. T1WI anti-phase diffuse signal reduction and post-enhanced hypovascular withdrawal enhancement patterns can aid in accurately diagnosing the disease condition.
Assuntos
Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Feminino , Humanos , Masculino , Adenoma de Células Hepáticas/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Meios de Contraste , Gadolínio DTPA , Fator 1-alfa Nuclear de Hepatócito , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Adolescente , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Stroke is the second leading cause of death worldwide. Understanding of gene expression dynamics could bring new approaches in diagnostics and therapy of stroke. Small noncoding molecules termed 'microRNA' represent the most flexible network of gene expression regulators. To screen out miRNAs that are mainly regulated during reperfusion in mechanically embolized patients, and study their mechanisms of action in reperfusion injury after thrombectomy, in order to find new therapeutic targets for mechanically embolized patients. Serums from 30 patients with moderate to severe stroke after mechanical thrombectomy (MT) were collected to measure miRNA expressions. Clinical information of patients was analyze, and patients were divided into poor prognosis and good prognosis. Factors affecting prognosis was classified, and independent risk factors for poor prognosis were determined. Prognostic value of National Institutes of Health Stroke Scale (NIHSS) score on admission to patients with MT was assessed. ROC (receiver operating characteristic) curves were drawn, and Kaplan-Merier method determined whether different NIHSS scores at admission had any difference in the in-hospital survival rate of consistency index/random consistency index (CI/RI) patients treated with MT. An oxygen-glucose deprivation/reperfusion (OGD/R) cell model and an middle cerebral artery occlusion (MCAO)/reperfusion mouse model were established, in which miR-298 expression was tested. In OGD/R cells, proliferation, apoptosis, and autophagy were assessed after intervention with miR-298 and/or autophagy related gene 5 (ATG5). In MCAO mice, the infarct area was calculated, and neurological function was assessed. The relationship between miR-298 and ATG5 was explored and validated. Age, diabetes, hypertension, hemorrhage transformation, NIHSS score at admission, leukocyte, neutrophil count and neutrophil to lymphocyte ratio (NLR) level were associated with patient's prognosis. Diabetes, NIHSS score at admission, and hemorrhagic transformation were independent risk factors for predicting poor prognosis in patients treated with MT. NIHSS score on admission had a predictive value on patient's prognosis. miR-298 was upregulated in acute cerebral ischemia patients with MT (p<0.05), especially in those with poor prognosis. miR-298 was elevated in both cell and mouse models (p<0.05). Apoptosis and autophagy of cells were weakened after miR-298 knockdown, and infarction in the mouse brain tissues was reduced. ATG5 was a target of miR-298. Overexpressing ATG5 rescued miR-298-induced apoptosis and autophagy. In conclusion: regulation of miR-298 and ATG5 attenuates neuronal apoptosis and autophagy, providing a new strategy for brain injury after reperfusion in patients with MT.
Assuntos
Apoptose , MicroRNAs , Traumatismo por Reperfusão , Trombectomia , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Humanos , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Trombectomia/métodos , Traumatismo por Reperfusão/metabolismo , Camundongos , Infarto da Artéria Cerebral Média/cirurgia , Infarto da Artéria Cerebral Média/metabolismo , Camundongos Endogâmicos C57BL , Autofagia/fisiologia , Prognóstico , Acidente Vascular CerebralRESUMO
The widespread application of QR code technology is best represented by the health codes used in China's pandemic prevention and control. This technology has enhanced the country's ability to manage the pandemic by achieving higher efficiency and accuracy. Unfortunately, a certain segment of the older population has encountered difficulties in adapting and maintaining their daily activities. This indicates the limitations of QR code technology in achieving social isolation. This article argues that for a more comprehensive pandemic prevention and control policy system to be established, managing the implementation of this very technology should be done in a more humane fashion, i.e. under the guidance of three moral principles: benevolence, justice, and non-maleficence. By doing so, implementation of QR code technology is done in a way that is not only conducive to COVID-19 prevention and control but also mitigate marginalization of the older people. In the post-pandemic era, the socialization of digital technology will accelerate. Therefore, in the field of public health, we should direct attention not only to the fair distribution of resources but also to the issue of identity that arises due to digital divide.
Assuntos
COVID-19 , Pandemias , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Idoso , Pandemias/ética , Justiça Social , Beneficência , Tecnologia Digital , Isolamento Social , Saúde Pública/ética , Princípios MoraisRESUMO
Objective: Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . Methods: Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. Results: In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion: BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.
Assuntos
Anticorpos Biespecíficos , Imunoterapia Adotiva , Humanos , Masculino , Adulto , Feminino , Anticorpos Biespecíficos/administração & dosagem , Pessoa de Meia-Idade , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Adulto Jovem , Idoso , Resultado do Tratamento , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
Objective: To explore the clinical effects of early rehabilitation treatment after repair surgery of skin and soft tissue defects accompanied by extensor tendon injury on the back of hand. Methods: This study was a retrospective non-randomized controlled study. From February 2015 to February 2023, 24 patients (15 males and 9 females, aged 12-55 years) with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand, who met the inclusion criteria and were repaired with flap transplantation and tendon grafting or tendon anastomosis, were admitted to the First Affiliated Hospital of Air Force Medical University. According to different intervention time for postoperative rehabilitation treatment of patients, the patients were divided into conventional rehabilitation group and early rehabilitation group, with 12 cases in each group. Patients in early rehabilitation group received rehabilitation treatment immediately after surgery under the rehabilitation guidance of specialized rehabilitation physicians based on the characteristics of different postoperative periods. Patients in conventional rehabilitation group began rehabilitation treatment from the third week after surgery, and their rehabilitation treatment was the same as that of patients in early rehabilitation group from the second week after surgery. The patients in 2 groups were treated in the hospital until the sixth week after surgery. The occurrence of flap vascular crisis and tendon rupture were observed within 6 weeks after surgery. After 6 weeks of surgery, the manual muscle test was used to measure the pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, and grip force of the affected hand; the total action motion method was used to evaluate the finger joint range of motion of the affected hand, and the excellent and good ratio was calculated; the Carroll upper extremity function test was used to score and rate the function of the affected hand. Results: Within 6 weeks after surgery, only 1 patient in conventional rehabilitation group suffered from venous crisis, and the flap survived after the second surgical exploration and anastomosis of blood vessels; there was no occurrence of tendon rupture in patients of 2 groups. After 6 weeks of surgery, there were no statistically significant differences in pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, or grip force of the affected hand between the two groups of patients (P>0.05); the excellent and good ratio of the finger joint range of motion of the affected hand of patients in early rehabilitation group was 11/12, which was higher than 7/12 in conventional rehabilitation group, but there was no statistically significant difference (P>0.05); the affected hand function score of patients in early rehabilitation group was 90±6, which was significantly higher than 83±8 in conventional rehabilitation group (t=2.41, P<0.05); the function rating of the affected hand of patients in early rehabilitation group was obviously better than that in conventional rehabilitation group (Z=2.04, P<0.05). Conclusions: Early rehabilitation treatment for patients with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand after repair surgery can improve hand function, but it would not increase surgery related complications, which is worthy of clinical promotion and application.
Assuntos
Lesões dos Tecidos Moles , Retalhos Cirúrgicos , Traumatismos dos Tendões , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Traumatismos dos Tendões/reabilitação , Traumatismos dos Tendões/cirurgia , Pessoa de Meia-Idade , Lesões dos Tecidos Moles/cirurgia , Lesões dos Tecidos Moles/reabilitação , Retalhos Cirúrgicos/cirurgia , Adolescente , Traumatismos da Mão/cirurgia , Traumatismos da Mão/reabilitação , Adulto Jovem , Mãos/cirurgia , Criança , Pele/lesões , Tendões/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodosRESUMO
Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging. Results: Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion: Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Biópsia/métodos , Antígeno Carcinoembrionário/sangue , Resultado do Tratamento , Adulto , IdosoRESUMO
Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-and-eosin-stained whole-slide images (WSIs). We trained an SSL Barlow Twins-encoder on 435 TCGA colon adenocarcinoma WSIs to extract features from small image patches. Leiden community detection then grouped tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival was confirmed in an independent clinical trial cohort (N=1213 WSIs). This unbiased atlas resulted in 47 HPCs displaying unique and sharing clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analysis of these HPCs, including immune landscape and gene set enrichment analysis, and association to clinical outcomes, we shed light on the factors influencing survival and responses to treatments like standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil new insights and aid decision-making and personalized treatments for colon cancer patients.