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Objective: To investigate the effect of the ratio of the maximum diameter of aneurysm sac to age (R) on the long-term efficacy of endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in patients with infrarenal abdominal aortic aneurysm (IAAA). Methods: This is a retrospective cohort study.The clinical data of 317 patients with IAAA who underwent surgical repair in the Department of Vascular Surgery,the Third Affiliated Hospital of Sun Yat-Sen University from January 2016 to October 2022 were retrospectively collected.There were 266 males and 51 females,aged (69.7±8.3) years (range:37 to 87 years).The R value of the patient was calculated and the receiver operating characteristic(ROC) curve was used to establish a model to calculate the optimal cut-off value.The propensity score matching method was used to match the baseline data of patients in the EVAR and OSR group by 3â¶1 (the caliper value was 0.05),and the patients were stratified according to the cutoff value of R, and the postoperative efficacy and survival of the patients were analyzed.The primary endpoint was the total mortality rate,and the secondary endpoints included the occurrence of postoperative complications and reintervention.Pearson χ2 or Fisher 's exact test was used for categorical variables, and independent sample t test or Wilcoxon rank sum test was used for continuous variables to compare differences between groups.The survival curves of the two groups were described by Kaplan-Meier method. Results: After propensity score matching,198 cases were in the EVAR group and 66 cases were in the OSR group.The ROC model showed that the best cut-off value of R value was 0.90,and the two groups were divided into two layers:R<0.90 and R≥0.90.Among them,112 patients with R<0.90 (84 cases of EVAR,28 cases of OSR);there were 152 patients with R≥0.90 (114 cases of EVAR and 38 cases of OSR).The follow-up time was (23.6±1.6) months (range:1 to 70 months).In the R≥0.90 stratification,the total mortality (26.3% vs.5.3%,χ2=7.600ï¼P=0.006),complication rate (44.7% vs.26.3%, χ2=4.025ï¼P=0.045), and secondary intervention rate (31.6% vs.13.2%, χ2=4.910ï¼P=0.027) in the EVAR group were higher than those in the OSR group.In the R<0.90 stratification,there was no significant difference in the total mortality rate (13.1% vs.10.7%, χ2=0.109ï¼P=0.741), complication rate (28.6% vs.35.7%, χ2=0.507ï¼P=0.477) and secondary intervention rate (14.3% vs.21.4%, χ2=0.353ï¼P=0.552) between the two groups. Conclusions: When R≥0.90 in IAAA patients,OSR maybe more beneficial to patients in terms of survival rate,postoperative complication rate and secondary intervention rate than EVAR.When R<0.90,there are no significant differences in survival rate,complication rate and secondary intervention rate between the two surgical methods.
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Aneurisma da Aorta Abdominal , Procedimentos Endovasculares , Humanos , Aneurisma da Aorta Abdominal/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Procedimentos Endovasculares/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Resultado do Tratamento , Adulto , Implante de Prótese Vascular/métodos , Fatores Etários , Pontuação de Propensão , Complicações Pós-OperatóriasRESUMO
Objective: To study the effects of periodontitis on bone and tryptophan metabolism of gut microbiota in the context of estrogen deficiency. Methods: Thirty-two female C57BL6/J mice were randomly divided into four groups based on table of random numbers (n=8 in each group): Sham group, in which mice were given sham surgery; Sham_Lig group, in which mice were given sham surgery and were induced to periodontitis by ligating the bilateral maxillary second molars with 5-0 silk threads at the fourth week; Ovx group, in which mice were given bilateral ovariectomy; Ovx_Lig group, in which mice were given bilateral ovariectomy and were induced to periodontitis at the fourth week. After 8 weeks of ligation, the mice of 4 groups were euthanized for collecting the samples of femur, tibia, mandible and skull. Those samples were scanned by micro-CT to measure the bone mineral density (BMD), bone volume versus total volume ratio (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp). The cecum contents of 4 groups of mice were collected for gut microbiota 16S rRNA gene sequencing. The tryptophan and its metabolites in intestinal tracts were detected by liquid chromatography-mass spectrometry. Pearson correlation analysis was performed to analyze the correlation between the abundance of gut microbiota and the content of tryptophan and its metabolites. Results: Femur BMD [(82.23±3.97) mg/cm3], BV/TV [(9.25±1.37)%] and Tb.Th [(70.95±5.70) µm] in Ovx_Lig group were significantly lower than Ovx group [(96.30±3.76) mg/cm3 (P=0.004); (14.45±1.55)% (P=0.022) and (87.58±8.02) µm (P<0.001), respectively]. The ß-diversity analysis of gut microbiota based on Bray-Curtis distance showed that samples of Ovx_Lig group and Ovx group were obviously grouped. Linear discriminant analysis effect size (LEfSe) showed that Alistipes was the representative genus in Ovx_Lig group. The relative abundance of Alistipes in Ovx_Lig group [(0.42±0.14)%] were significantly higher than that in Ovx group [(0.17±0.05)%] (t=4.45, P<0.001). Tryptophan metabolism analysis showed that the content of kynurenic acid [(531.12±158.60) ng/g] in Ovx_Lig group were significantly higher than that in Ovx group [(400.42±57.96) ng/g] (t=2.19, P=0.046). And the content of indole-3-carbaldehyde [(383.37±144.06) ng/g] in Ovx_Lig group were significantly lower than Ovx group [(701.72±141.93) ng/g] (t=4.45, P<0.001). Correlation analysis showed that relative abundance of Alistipes was positively correlated with kynurenic acid (r=0.32, P=0.088), while negatively correlated with indole-3-carbaldehyde (r=-0.32, P=0.088). Conclusions: Periodontitis can induce bone destruction of femur in estrogen-deficient mice, the mechanism of which may be related to Alistipes in gut and the tryptophan metabolites kynurenic acid and indole-3-carbaldehyde.
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Microbioma Gastrointestinal , Osteoporose , Periodontite , Animais , Feminino , Camundongos , Densidade Óssea , Estrogênios , Ácido Cinurênico , Ovariectomia , RNA Ribossômico 16S , TriptofanoRESUMO
Cyclic GMP-AMP synthase (cGAS) is a DNA receptor that produces the second messenger cyclic GMP-AMP (cGAMP). cGAMP activates stimulator of interferon genes (STING), which initiates a signaling cascade leading to immune and inflammatory responses. This intricate molecular pathway plays a pivotal role in the pathogenesis and progression of diverse respiratory ailments, including respiratory infection, lung cancer, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, asthma, and acute lung injury. Consequently, the cGAS-STING signaling pathway has emerged as a promising novel therapeutic target, opening up new avenues for the diagnosis and treatment of respiratory disorders. This review focuses on recent advances in our understanding of the cGAS-STING signaling pathway and its intricate involvement in respiratory system diseases.
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Nucleotídeos Cíclicos , Transtornos Respiratórios , Infecções Respiratórias , Humanos , Nucleotidiltransferases/genética , InterferonsRESUMO
Objective: To investigate the efficacy and safety of modified Bikini approach periacetabular osteotomy in the treatment of developmental hip dysplasia under 50 years of age. Methods: The clinical data of 39 patients with developmental hip dysplasia who underwent periacetabular osteotomy in the Department of Orthopedics, Guizhou Provincial People's Hospital from June 2016 to June 2021 were retrospectively analyzed.Among them, 20 patients (21 hips) underwent the improved Bikini approach (study group) and 19 patients (20 hips) underwent the improved Smith-Petersen approach (control group).In the study group, there were 3 males and 17 females, aged(M(IQR))27.5 (14.3) years (range:11 to 44 years).In the control group, there were 2 males and 17 females, aged 27.5 (19.3) years (range:17 to 47 years).Both groups were sutured in the same manner by the same physician.Incision length, operation time, intraoperative blood loss and complications were recorded.X-ray images, anterior central marginal angle (ACE), lateral central marginal Angle (LCE) and acetabulum tilt angle (Tonnis AI) were measured before and after the operation.The coverage rate of acetabulum to femoral head (AHI) was measured and calculated, and the healing time was observed.Harris Hip score, International Hip score (IHOT)-12 and visual analogue scale (VAS) were recorded before and after surgery.Vancouver Scar Scale (VSS) score and patient and observer scar assessment scale (POSAS) score were recorded 12 months after surgery.The independent sample t test,Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All patients successfully completed the operation.There was no significant difference in operation time and intraoperative blood loss between the two groups (all P>0.05).The incision length of the study group was smaller than that of the control group, and the difference was statistically significant (10.5(5.0)cm vs.15.0(3.0),W=309.000,P=0.007).Patients were followed up for (19.1±11.1) months (range:12 to 60 months).Femoral nerve stretching injury occurred in 2 cases and sciatic branch fracture occurred in 1 case in the study group, all of which recovered to normal at 3 months follow-up, while no corresponding injury occurred in the control group.Lateral femoral cutaneous nerve injury occurred in 3 cases in the study group and 2 cases in the control group.Delayed wound healing occurred in 1 case in each of the two groups, and both healed after re-operation debridement and suture.Pubic branch nonunion occurred in 4 patients in the study group and 5 patients in the control group.There were no serious complications such as sciatic nerve and femoral blood vessel injury between the 2 groups, and there was no statistical significance in the incidence of complications between the 2 groups (52.4%(11/21)vs.40.0%(8/20),χ2=0.631,P=0.427).The clinical healing time of the patient was (4.5±1.3) months after surgery (range:3.0 to 8.0 months).There were no significant differences in ACE, LCE, Tonnis AI and AHI between the 2 groups (all P>0.05).At the last follow-up, there were no significant differences in VAS,Harris hip score and IHOT-12 score between the two groups (all P>0.05).The incision scars in the study group were smaller than those in the control group, and the differences in VSS and POSAS were statistically significant (all P<0.05). Conclusion: Compared with the improved Smith-Petersen approach, the improved Bikini approach has the same early clinical efficacy in the treatment of patients with developmental hip dysplasia under the age of 50, and has the advantages of smaller postoperative incision scars, more hidden and beautiful incision, and no serious complications, which is worthy of further study and promotion.
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Objective: To analyze the clinicopathological characteristics of IgG4-related sialadenitis (IgG4-RS). Methods: A total of 40 cases diagnosed with IgG4-RS were collected from the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2019 to December 2022. Among them, there were 26 males and 14 females. The age range was 29-77 years old [(59.4±11.8) years old], with 23 patients being older than 60 years. The lesion site, imaging manifestations, histopathological features, serological test and treatment information of patients were collected. The expression of IgG4 and IgG proteins was detected by immunohistochemistry. Results: Submandibular region swelling was the most common initial symptom of IgG4-RS (38/40, 95.0%). All the patients having serum IgG4 levels> 1.35 g/L. Serum IgG4 levels were significantly increased in patients aged>60 years (Z=-2.45, P=0.014) and those involving multiple glands (Z=-2.04, P=0.042). Thirty six cases received major salivary gland biopsy, and all the cases showed dense lymphocyte and plasma cell infiltration. Lymphoid follicle, storiform fibrosis and obliterative phlebitis were seen in 88.9% (32/36), 63.9% (23/36), 30.6% (11/36) of the cases, respectively. Twenty one cases received labial salivary gland biopsy, 66.7% (14/21) showed lymphocyte and plasma cell infiltration, 19.0% (4/21) had lymphoid follicle structures, and 33.3% (7/21) showed no obvious histological abnormalities. No signs of fibrosis or obliterative phlebitis were observed in all labial salivary gland biopsies. And 95.0% (38/40) of cases had IgG4 positive plasma cell>10/HPF, 82.5% (33/40) of cases had IgG4/IgG positive plasma cell ratio>40%. All the patients had a decrease in serum IgG4 levels after glucocorticoid treatment, but only 21.4% (6/28) of cases had reduced to normal levels (≤1.35 g/L), and there were still significant fluctuations in serum IgG4 levels thereafter. Conclusions: IgG4-RS has a predilection for middle-aged and elderly male patients, and serum IgG4 levels are significantly related to the patient's age and whether multiple glands are involved. Labial salivary gland biopsy cannot replace submandibular gland for histopathological evaluation. It is a common phenomenon that serum IgG4 levels cannot restored to normal levels after glucocorticoid treatment. This study provides certain assistance for clinical and pathological diagnosis of IgG4-RS. This study is beneficial for further understanding IgG4-RS and improving the clinical and pathological diagnosis of the disease.
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Flebite , Sialadenite , Pessoa de Meia-Idade , Idoso , Feminino , Humanos , Masculino , Adulto , Glucocorticoides , Imunoglobulina G/uso terapêutico , China , Sialadenite/diagnóstico , Sialadenite/patologia , Inflamação/tratamento farmacológico , Fibrose , Flebite/tratamento farmacológicoRESUMO
Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.
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Antineoplásicos Imunológicos , Inibidores de Checkpoint Imunológico , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Fígado , Glucocorticoides/uso terapêuticoRESUMO
Virtual reality is a form of high-fidelity simulation that may be used to enhance the quality of medical education. We created a bespoke virtual reality trainer software using high resolution motion capture and ultrasound imagery to teach cognitive-motor needling skills necessary for the performance of ultrasound-guided regional anaesthesia. The primary objective of this study was to determine the construct validity between novice and experienced regional anaesthetists. Secondary objectives were: to create learning curves for needling performance; compare the virtual environment immersion with other high-fidelity virtual reality software; and compare cognitive task loads imposed by the virtual trainer compared with real-life medical procedures. We recruited 21 novice and 15 experienced participants, each of whom performed 40 needling attempts on four different virtual nerve targets. Performance scores for each attempt were calculated based on measured metrics (needle angulation, withdrawals, time taken) and compared between the groups. The degree of virtual reality immersion was measured using the Presence Questionnaire, and cognitive burden was measured using the NASA-Task Load Index. Scores by experienced participants were significantly higher than novices (p = 0.002) and for each nerve target (84% vs. 77%, p = 0.002; 86% vs. 79%, p = 0.003; 87% vs. 81%, p = 0.002; 87% vs. 80%, p = 0.003). Log-log transformed learning curves demonstrated individual variability in performance over time. The virtual reality trainer was rated as being comparably immersive to other high-fidelity virtual reality software in the realism, possibility to act and quality of interface subscales (all p > 0.06) but not in the possibility to examine and self-performance subscales (all p < 0.009). The virtual reality trainer created workloads similar to those reported in real-life procedural medicine (p = 0.53). This study achieved initial validation of our new virtual reality trainer and allows progression to a planned definitive trial that will compare the effectiveness of virtual reality training on real-life regional anaesthesia performance.
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Laparoscopia , Realidade Virtual , Humanos , Competência Clínica , Simulação por Computador , Software , Ultrassonografia de Intervenção , Interface Usuário-ComputadorRESUMO
A male neonate who was unable to open both eyes with the adhesion of upper and lower palpebral margins since birth was clinically diagnosed as bilateral ankyloblepharon filiforme adnatum. The fused eyelids were divided surgically under general anesthesia. The neonate can open and close eyes normally with right positions of eyelids and flexible movements of eyeballs to follow light after the surgery.
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Anormalidades do Olho , Pálpebras , Humanos , Recém-Nascido , Masculino , Pálpebras/patologia , Pálpebras/cirurgia , Anormalidades do Olho/cirurgiaRESUMO
BACKGROUND: Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in antiangiogenesis which has been an essential strategy for cancer treatment. We report the first-in-human study of AK109, a novel anti-VEGFR2 monoclonal antibody, to characterize the safety profile and pharmacokinetics/pharmacodynamics (PK/PD) properties, and explore the preliminary antitumor efficacy in patients with solid tumors. PATIENTS AND METHODS: This was a multicenter, open-label, phase I study, including dose escalation and dose expansion (NCT04547205). Patients with advanced cancers were treated 2 and 3 weekly with escalating doses of AK109. A 3 + 3 design was used to determine the maximum tolerated dose. Blood was sampled for PK/PD analysis. The primary endpoint was safety and recommended phase II dose (RP2D). RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed. However, 38 patients reported treatment-related adverse events (TRAEs); grade ≥3 TRAEs occurred in 10 patients. The most common TRAEs were proteinuria (n = 24, 60%), hypertension (n = 13, 32.5%), increased aspartate transaminase (n = 11, 27.5%), thrombopenia (n = 10, 25%), and anemia (n = 10, 25%). A total of 28 patients (70%) reported adverse events of special interest (AESIs). The most common AESIs were proteinuria (60%), hypertension (32.5%), and hemorrhage (32.5%), mainly including gum bleeding and urethrorrhagia. AK109 exhibited an approximately linear PK exposure with dose escalation at 2-12 mg/kg. PD analyses showed rapid target engagement. Among the 40 patients, 4 achieved partial response and 21 achieved stable disease with an objective response rate of 10% and a disease control rate of 62.5%. Based on the safety profile, the PK/PD profile, and preliminary antitumor activities, 12 mg/kg Q2W and 15 mg/kg Q3W were selected as RP2D. CONCLUSIONS: AK109 showed manageable safety profile and promising antitumor activity, supporting further clinical development in a large population.
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Neoplasias , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Neoplasias/patologiaRESUMO
Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients (P=0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.
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A 71-year-old man presented with a history of persistent redness and swelling in the left eye accompanied by an enlarging mass in the conjunctiva. He denied any history of trauma. Local anti-inflammatory treatment was ineffective. Slit lamp examination demonstrated a tough and immobile grayish broad basal mass at the corneal limbus and bulbar conjunctiva and a local bulge of 3 mm × 2 mm at the medial and lateral side of the upper palpebral conjunctiva near the eyelid margin. The excisional biopsy showed granulomatous inflammation with irregular and atypical squamous epithelial hyperplasia. Histopathology and immunohistochemical staining revealed a fungal infection. The secretion smear examination was performed to clarify the pathogen as Candida albicans, and chronic fungal maxillary sinusitis was found through imaging tests. Thus a diagnosis of conjunctival candidiasis was made. The conjunctival mass subsided after systemic and local antifungal therapy.
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Humanos , IdosoRESUMO
Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P<0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P<0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference (P=0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) (OR=3.39, 95%CI: 1.59-7.21), dual-marker ASCA (+) ANCA (-) (OR=2.87, 95%CI: 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) (OR=3.09, 95%CI: 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) (OR=3.15, 95%CI: 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) (OR=2.69, 95%CI: 1.42-5.12) and dual-marker ANCA (+) ASCA (-) (OR=2.11, 95%CI: 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Masculino , Feminino , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Constrição Patológica , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Autoanticorpos , Fenótipo , BiomarcadoresRESUMO
Objective: To evaluate the short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients with moderate and severe active IBD at the first use of vedolizumab from May 1 to October 31, 2021 were retrospectively enrolled. Then the clinical characteristics, and the efficacy and safety of vedolizumab were evaluated. Meanwhile, the clinical response rate, biological response rate and endoscopic response rate were calculated. Multivariate analysis was used to evaluate the independent influencing factors of short-term clinical efficacy and safety. Results: A total of 78 patients (44 males and 34 females) with IBD were enrolled, with a mean age of (40.5±11.9) years. The clinical remission rate, clinical response rate, biological remission rate, biological response rate and endoscopic remission rate was 60.3% (47/78), 85.9% (67/78), 70.5% (55/78), 43.6% (34/78) and 47.0% (31/66) respectively after 14 weeks of treatment. Body mass index (BMI) ≥ 18.5 kg/m2 (HR=5.04, 95%CI: 1.50-16.91, P=0.009) and biological remission at 6 weeks of treatment (HR=15.22, 95%CI: 3.16-73.38, P=0.001) were predictors of endoscopic remission at 14 weeks of treatment. Adverse reactions occurred in 57 patients, with an incidence of 73.1%. The main manifestations were liver and kidney damage (37.2%) and infection (26.9%). Conclusions: More than half of patients with moderate and severe active IBD can achieve clinical remission after 14 weeks of vedolizumab treatment. Baseline BMI level and biological remission at 6 weeks of treatment are predictors of mucosal healing at 14 weeks. The incidence of adverse reactions is not low, although serious adverse reactions are rare in short-term treatment.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Fármacos Gastrointestinais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Indução de Remissão , Doenças Inflamatórias Intestinais/tratamento farmacológico , Resultado do Tratamento , Doença CrônicaRESUMO
Objective: To investigate the potential independent risk factors of body mass rebound following laparoscopic sleeve gastrectomy (LSG) and construct a nomogram prediction model based on these factors. Methods: In this retrospective observational study, patients with obesity who had undergone LSG at the Department of Gastrointestinal Surgery of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University between January 2015 and July 2017 were retrospectively enrolled. These patients were divided according to their status of postoperative body mass rebound. The inclusion criteria were patients aged between 16 and 65 years who had undergone LSG bariatric surgery with surgical indications according to the 2014 Chinese Guidelines for the Surgical Management of Obesity and Type 2 Diabetes Mellitus. The exclusion criteria were patients who had undergone other bariatric surgeries, who were taking weight-loss drugs or drugs that affected their body weight, who had severe gastroesophageal reflux and hiatal hernia, who were pregnant, who had incomplete clinical data, and who were lost to follow-up or were followed up for <3 years. In total, 241 patients with obesity (69 males and 172 females) who had undergone LSG surgery were enrolled. The mean age and body mass index (BMI) were (29.9±5.8) years and (40.8±4.8) kg/m2, respectively. The patients were followed up till July 2022, with a focus on their body weight. Postoperative body mass rebound was defined as a percentage increase of ≥10% from the nadir body mass, which was the lowest body mass during the 3-year follow-up period. The body weight rebound following LSG and its influencing factors were observed, based on which a nomogram model was constructed and evaluated. The relationships between the patients' basic data, clinical indicators, preoperative hematological indicators, postoperative indicators, and body weight rebound following LSG were analyzed via univariate analysis. Independent risk factors were further screened by multivariate logistic regression analysis. Factors with a statistically significant difference were included into the nomogram prediction model. Moreover, the model was internally (modeling set) and externally (validation set, 80 baseline data-matched patients with obesity from our center) validated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) via R software. ROC curve analysis was used to analyze the predictive and cutoff values of the measurement data for body mass rebound. Results: Overall, 90 patients (37.3%) exhibited postoperative body weight rebound, with the lowest BMI of (29.5±2.6) kg/m2 and time to reach the lowest BMI of (15.4±2.3) months; 151 patients (62.7%) did not exhibit body weight rebound, with the lowest BMI of (29.8±2.3) kg/m2 and time to reach the lowest BMI of (14.7±2.1) months. The results of univariate analysis showed that BMI, depression, anxiety, C-reactive protein (CRP) levels, systemic immune inflammatory index (SII), prognostic nutritional index (PNI), and albumin/fibrinogen ratio (AFR) were associated with body weight rebound following LSG with statistically significant differences (all P<0.05). The results of multivariate regression analyses suggested that depression [odds ration (OR) = 1.31, 95% confidence interval (CI): 1.08-1.62, P=0.010], preoperative CRP levels of ≥8 mg/L (OR = 1.34, 95% CI: 1.09-1.69, P=0.007), SII (OR = 0.58, 95% CI: 0.41-0.86, P=0.013), PNI (OR = 2.06, 95% CI: 1.03-4.21, P=0.007), and AFR (OR: 0.49, 95% CI: 0.33-0.69, P=0.011) were five independent risk factors for body mass rebound. A nomogram prediction model was constructed based on the multivariate analysis results. The scores of PNI, SII, AFR, CRP, and depression were 92.5, 100, 72.5, 25, and 27.5, respectively. The total score was calculated by adding the individual scores of each risk factor, which was used to calculate the probability of body mass rebound following LSG. The evaluation results of the nomogram model showed a C-index of 0.713 and 0.762, sensitivity of 0.656 and 0.594, and specificity of 0.715 and 0.909 in the modeling and validation sets, respectively. The calibration curve analysis and DCA indicated that the nomogram model has a good predictive value for body mass rebound after LSG. Conclusion: Preoperative depression, CRP of ≥8 mg/L, SII, PNI, and AFR were independent risk factors for body mass rebound following LSG. Hence, the nomogram prediction model based on these factors can effectively predict body mass rebound in patients undergoing LSG.
Assuntos
Fármacos Antiobesidade , Diabetes Mellitus Tipo 2 , Laparoscopia , Adolescente , Adulto , Idoso , Proteína C-Reativa , Análise Fatorial , Feminino , Fibrinogênio , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Nomogramas , Obesidade , Estudos Retrospectivos , Fatores de Risco , Redução de Peso , Adulto JovemRESUMO
Objective: To analyze the effects and mechanisms of three commonly used epidural coverings, gelatin sponge, bovine Achilles tendon extract collagen and polyester urethane fiber, in preventing epidural scar adhesions after laminectomy in rats. Methods: Forty-eight adult Wistar rats were excised from L2 to L5 lamina to establish laminectomy models, and were divided into four groups with random number table according to different covering materials (12 rats in each group): blank group (group A), gelatin sponge group (absorbable, group B), polyester urethane fiber group (non-absorbable, group C) and bovine Achilles tendon extract collagen group (absorbable, group D). At 4 and 12 weeks postoperatively, the spinal tissues of the operated area were taken for gross observation (Rydell scar adhesion rating criteria) and histological observation (Nussbaum criteria); and the expression of three scar proliferation-related cytokines, basic fibroblast growth factor (bFGF), growth transforming factor ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF), were measured in the peridural tissues. The differences between the indices in each group were analyzed and compared. Results: All 48 rats survived, and gross and histological findings at 4 and 12 weeks showed no dural adhesions in the gelatin sponge and bovine Achilles tendon extract collagen groups, adhesions in the polyester urethane fiber group, and heavy adhesions and spinal cord compression in the blank control group. There were significant differences in the Rydell grade and Nussbaum histological score between the absorbable material group and the non-absorbable group (both P<0.05). Western protein blotting at 4 and 12 weeks confirmed that the expression levels of three cytokines, including bFGF, TGF-ß1, and VEGF, were lower in the absorbable material group than those in the non-absorbable group (all P<0.01). Immunofluorescence tests at 12 weeks confirmed that the expression of bFGF, TGF-ß1 and VEGF were all lower in the gelatin sponge group (9.81±0.81, 12.42±2.35, 8.63±1.76) and the bovine Achilles tendon extract collagen group (12.70±2.02, 8.23±1.03, 10.19±2.67) than those in the polyester urethane fiber group (33.94±2.03, 30.29±2.76, 25.79±1.21) (all P<0.01). Conclusions: Bovine achilles tendon extract collagen and gelatin sponge can effectively reduce the hyperplasia of scar and dural adhesions after spinal surgery.
Assuntos
Cicatriz , Fator A de Crescimento do Endotélio Vascular , Animais , Bovinos , Cicatriz/patologia , Cicatriz/prevenção & controle , Colágeno/metabolismo , Gelatina , Hiperplasia , Laminectomia , Poliésteres , Ratos , Ratos Wistar , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle , Fator de Crescimento Transformador beta1/metabolismo , UretanaRESUMO
Objective: To compare the difference of decentration and tilt among 4 kinds of aspherical intraocular lenses (IOLs), and to analyze their objective visual quality. Methods: Prospective non-randomized controlled clinical trial. Age-related cataract patients who planned to undergo phacoemulsification and IOL implantation in the Affiliated Hospital of North Sichuan Medical College from April to June in 2020 were divided into ZCB00 group, SN60WF group, A1-UV group, and AO group according to IOL types. Thirty right eyes and thirty left eyes were selected in each group. Before operation and at 1 day, 1 week and 1 month postoperatively, decentration and tilt values were measured by a new swept-source anterior-segment optical coherence tomography device (CASIA2), and wavefront aberrations, objective scatter index (OSI), modulation transfer function cut off frequency (MTF cut off) and Strehl ratio (SR) were also examined. Values of decentration, tilt and visual quality compared among 4 groups were took from the right eye. One-way analysis of variance was used for inter-group comparison, and repeated measurement one-way analysis of variance was used for intra-group comparison. Data between right eyes and left eyes from all the individuals were compared by independent sample t-test. Results: A total of 181 patients (240 eyes) were enrolled, and 169 patients (224 eyes) completed the follow-up (114 right eyes and 110 left eyes). There were 77 males and 92 females, with an age of (69±9) years. There was no significant difference in gender, age, axial length, decentration and tilt of crystalline lens and IOL power among 4 groups (all P>0.05). At 1 day, 1 week and 1 month postoperatively, there was significant difference in decentration value among 4 groups (F=7.11, 6.12, 4.66; all P<0.05). For further pairwise comparison, the decentration value of SN60WF group was higher than that of the other 3 groups at 1 day and 1 week postoperatively, and the decentration value of SN60WF group was (0.259±0.101) mm at 1 month postoperatively, which was higher than that of ZCB00 group (0.177±0.099) mm and AO group (0.163±0.122) mm, and the differences were statistically significant (using SNK-q test, both P<0.05). The IOL tilt value in the ZCB00 group, SN60WF group, A1-UV group, and AO group at 1 month postoperatively were (4.806±1.129)°, (5.080±1.309)°, (4.586±1.338)°, (5.112±1.406)°, respectively. No significant difference in tilt value among 4 groups was found at any time after surgery (all P>0.05). In each group, there was no significant difference in decentration and tilt value at different postoperative time points (all P>0.05). At 1 month postoperatively, there was no significant difference in decentration and tilt at horizontal and vertical directions respectively among 4 groups (all P>0.05), and in each group, there was no significant difference in decentration and tilt value between right eyes and left eyes (all P>0.05), and IOLs tended to tilt towards the inferonasal or inferotemporal direction in both eyes. With 4-mm and 6-mm pupil diameter, there was significant difference in internal (F=131.32, 85.17) and ocular (F=46.64, 47.55) spherical aberration among 4 groups (all P<0.01). For further pairwise comparison, the spherical aberration of AO group was higher than that of the other 3 groups, and the difference was statistically significant (using SNK-q test, all P<0.05). There was no significant difference in OSI, MTF cut off and SR among 4 groups (all P>0.05). Conclusions: The four types of IOLs show decentration and tilt in varying degrees after implantation in the capsular bag, but this difference do not lead to clinical significance. Human eyes have tolerance to mild decentration and tilt of aspheric IOLs, showing good visual quality.
Assuntos
Extração de Catarata , Lentes Intraoculares , Facoemulsificação , Idoso , Feminino , Humanos , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Objective: To evaluate the association between periodontitis and mild cognitive impairment (MCI), and explore the potential local oral risk factors for MCI. Methods: The study included 70 middle-aged and elderly subjects (44 females and 26 males) with periodontal disease who were first diagnosed by the Department of Periodontology or referred by the Department of Geriatrics in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2021 to January 2022. In this study, the control group consisted of periodontal disease patients without cognitive impairment, and the case group (MCI group) consisted of those diagnosed with MCI referred by the geriatrics specialists. Full-mouth periodontal examinations of all subjects were performed and periodontal indicators were recorded by periodontists, while digital panoramic radiographs were taken. The severity of periodontitis was defined according to the 1999 classification, and the staging and grading of periodontitis were defined according to the 2018 American Academy of Periodontology and European Federation of Periodontology classification. The mini-mental state examination scale was chosen by geriatricians to evaluate the cognitive function of the included subjects. The cubital venous blood was drawn to detect the expression levels of inflammatory factors such as hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α(TNF-α) in serum. Independent-samples t test and chi-square test were used to analyze the differences in population factors, periodontal-related indexes and serum inflammatory factors between the two groups (α=0.05). Odds ratios (OR) for MCI according to the severity of periodontitis and main periodontal clinical indexes were calculated by binary Logistic analysis. Results: Thirty-nine subjects were included in the control group and thirty-one in the MCI group. The age of the study population was (58.3±6.2) years (range: 45-70 years). The comparison between two groups showed that the control group was with higher educational background (χ²=9.45, P=0.024) and 2.6 years younger than the MCI group [(57.1±6.0) years vs. (59.7±6.3) years, t=-1.24, P=0.082]. The number and proportion of moderate to severe periodontitis in control group were significantly lower compared to those in MCI group (17 cases with 43.6% vs. 23 cases with 74.2%, χ²=6.61, P=0.010), and the OR of moderate to severe periodontitis adjusted by age and educational background was 3.00 (95%CI: 1.01-8.86, P=0.048). Compared with the grading (χ²=5.56, P=0.062) of periodontitis, staging had a greater impact on MCI (χ²=7.69, P=0.041), moreover the proportion of MCI in stage â grade A periodontitis was significantly lower than any other type of periodontitis (χ²=13.86, P=0.036). In addition, less presence of deep periodontal pockets [probing depth (PD)≥6 mm] (17.9% vs. 41.9%, χ²=4.87, P=0.027), fewer number of PD≥4 mm (6.48±6.70 vs. 11.03±8.91, t=-2.44, P=0.017), lower plaque index (1.42±0.56 vs. 1.68±0.57, t=-1.91, P=0.059) and gingival index (1.68±0.29 vs. 1.96±0.30, t=-3.93, P<0.001) were in the control group than in the MCI group. However, there were no significant differences between the two groups in the levels of serum inflammatory factors, such as hs-CRP, IL-1ß, IL-6 and TNF-α (P>0.05). Conclusions: It appears a strong correlation between moderate to severe periodontitis and the incidence of MCI in middle-aged and elderly people. Moreover, deep and increased number of periodontal pockets, poor oral hygiene, and severe gingival inflammation can be potentially associated risk factors for MCI.
Assuntos
Disfunção Cognitiva , Doenças Periodontais , Periodontite , Idoso , Proteína C-Reativa/análise , China , Disfunção Cognitiva/complicações , Feminino , Humanos , Interleucina-6 , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/complicações , Bolsa Periodontal , Periodontite/complicações , Projetos Piloto , Fator de Necrose Tumoral alfaRESUMO
Objective: To study the effects of salivary microbiota in patients with periodontitis on the tryptophan-aryl hydrocarbon receptor (AhR) signaling axis in mice with periodontitis and to provide theoretical basis as well as new ideas for the influences of periodontitis on systemic metabolism. Methods: Salivary microbiota of 12 healthy individuals and 14 patients with periodontitis were collected in Nanjing Stomatological Hospital, Medical School of Nanjing University from June to December of 2020. According to the random number table method, twenty-four mice were randomly divided into three groups: Sham group (control group), P group (periodontitis patients' salivary microbiota group) and H group (periodontal healthy individuals' salivary microbiota group). The maxillary second molars of all mice were treated with silk thread ligation to induce periodontitis. Phosphate buffer as well as salivary microbiota of periodontal healthy individuals and periodontitis patients were gavaged into periodontitis mice for 2 weeks. The expression of inflammatory factors in mice serum were detected by enzyme linked immunosorbent assay, and the expression of tryptophan and indole metabolites in intestinal tract and serum were detected by liquid chromatography-mass spectrometry. The expression of AhR in intestinal tract of mice was detected by immunohistochemistry and quantitative real time-PCR while gut microbiota constitution was detected by 16S rRNA gene sequencing. The remaining saliva samples of periodontitis patients and periodontal healthy individuals were applied to detect the expression of tryptophan and indole metabolites themselves. Results: The salivary microbiota of periodontitis patients could induce the expression of interleukin-1ß [P group: (162.38±39.46) pg/ml, H group: (82.83±20.01) pg/ml; t=4.40, P=0.001) and tumor necrosis factor-α [P group: (361.16±123.90) pg/ml, H group: (191.66±106.87) pg/ml; t=2.54, P=0.030) in serum of periodontitis mice, and reduce the expression of AhR in colon (P group: 1.18±0.05, H group:1.83±0.47; t=3.09, P=0.015) and ileum (P group: 0.80±0.13, H group: 1.18±0.11; t=4.93, P=0.001). After gavage of salivary microbiota of periodontitis patients to the mice, tryptophan (P group: (18.1±3.8)×107, H group: (26.6±6.6)×107; t=2.49, P=0.037] and indole lactic acid [P group: (1.9±0.7)×107, H group: (3.7±0.6)×107; t=4.49, P=0.002) in serum of periodontitis mice were significantly decreased, but was relatively disorder in intestinal tract. However, the expressions of tryptophan and indole metabolites in saliva of periodontitis patients were higher than those of periodontal healthy individuals. There were significant differences in indole propionic acid [P group: (1 239.39±818.72) nmol/L, H group: (56.96±38.33) nmol/L; t=2.83, P=0.022]. What we find noteworthy was that the expressions of indolelactic acid metabolism in saliva, serum and intestinal were consistent, and salivary microbiota of periodontitis patients could reduce the relative abundance of indolelactic acid-producing bacteria in the gut, suggesting that the salivary microbiota of periodontitis patients might affect the expression of AhR through gut microbiota disorder and indolelactic acid downregulation. Conclusions: Salivary microbiota in patients with periodontitis may affect the systemic inflammatory state through down-regulating the expression of tryptophan-AhR signal axis.
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Microbiota , Periodontite , Animais , Humanos , Indóis , Camundongos , Periodontite/microbiologia , RNA Ribossômico 16S/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Triptofano/metabolismoRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance frequently occurs in patients with non-small-cell lung cancer (NSCLC). EGFR Thr790Met mutation (T790M+) is seen in â¼50% of patients. We assessed the safety, tolerability, and pharmacokinetics (PK) of BPI-15086, a novel, ATP-competitive, irreversible, third-generation, mutation-selective EGFR-TKI in patients with EGFR T790M-mutated NSCLC. PATIENTS AND METHODS: This two-center, phase I, dose-escalation study included patients who were 18-65 years old, with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically or cytologically confirmed locally advanced or metastatic T790M+ NSCLC who were not surgical or radiotherapy candidates, and had imaging-identified disease progression after prior EGFR-TKIs. This dose-escalation study enrolled patients using a 3 + 3 study design. Patients received 25, 50, 100, 200, and 300 mg/day orally in 21-day cycles. The primary endpoints were safety, tolerability, and PK. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR). The dose-expansion study was not conducted. RESULTS: We enrolled 17 patients from 29 December 2016 to 16 May 2018, in the safety and full analysis sets. All patients completed a single dosing trial, and no adverse events (AEs) causing drug discontinuation were seen. Grade 1-2 nausea, hypoalbuminemia, and decreased appetite were the most common treatment-related AEs. Grade 3 hyperglycemia was seen in one patient dosed at 300 mg/day. The ORR and DCR were 17.7% [95% confidence interval (CI) 3.8% to 43.4%] and 47.1% (95% CI 23.0% to 72.2%), respectively. CONCLUSION: BPI-15086 is a safe and tolerable third-generation EGFR-TKI with a rationale for further clinical studies.