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2.
Public Health ; 230: 21-28, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484622

RESUMO

OBJECTIVES: The objective of this experiment was to evaluate the spatial pattern and temporal trend of colorectal cancer (CRC) burden attributed to dietary risk factors in China from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. METHODS: Numbers and age-standardised rates of deaths, disability-adjusted life years (DALYs) and corresponding average annual percentage change (AAPC) were determined. The joinpoint regression analysis was used to assess the temporal trends of CRC deaths and DALYs from 1990 to 2019. RESULTS: In China, the number of diet-attributable CRC deaths and DALYs in 2019 were 90.41 (95% uncertainty interval: 65.69, 114.67) and 2234.06 (1609.96, 2831.24) per-1000 population, marking 2.05% and 1.68% annual increases since 1990, respectively. The region with the highest increase in age-standardised rates (ASRs) of diet-related CRC deaths and DALYs was in Taiwan with an AAPC of 2.00% (1.51, 2.48), whereas the highest decline in ASRs of CRC deaths and DALYs was observed in Hong Kong with an AAPC of -0.63% (-0.90, -0.35) (all P < 0.05). Nationally, men suffered higher CRC deaths and DALY burdens attributable to dietary risks than did women. Regarding the specific diet group, diets low in calcium, milk, and whole grains contributed to CRC deaths and DALYs the most. CONCLUSIONS: Diet is an important contributor to increasing CRC burden in China. Necessary measures should be taken to kerb the growing burden attributed to dietary factors, particularly in males and in regions with middle Socio-demographic Index or lower.


Assuntos
Neoplasias Colorretais , Carga Global da Doença , Masculino , Humanos , Feminino , Fatores de Risco , Dieta/efeitos adversos , China/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Saúde Global , Neoplasias Colorretais/epidemiologia
4.
Clin Oncol (R Coll Radiol) ; 36(3): 157-164, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38262779

RESUMO

AIMS: Despite a largely successful 'zero COVID' policy in 2020, the COVID-19 pandemic disrupted routine cancer services in the city of Hong Kong. The aims of this study were to examine the trends in cancer incidence before and during the COVID-19 pandemic and estimate missed cancer diagnoses. MATERIALS AND METHODS: We used population-based data from the Hong Kong Cancer Registry 1983-2020 to examine the trends of age- and sex-standardised cancer incidence before and during the COVID-19 pandemic. We applied: (i) the annual average percentage change (AAPC) calculated using the Joinpoint regression model and (ii) the autoregressive integrated moving average (ARIMA) model to forecast cancer incidence rates in 2020. Missed cancer diagnoses in 2020 were estimated by comparing forecasted incidence rates to reported rates. A subgroup analysis was conducted by sex, age and cancer site. RESULTS: The cancer incidence in Hong Kong declined by 4.4% from 2019 to 2020 (male 8.1%; female 1.1%) compared with the long-term AAPC of 0.5% from 2005 to 2019 (95% confidence interval 0.3, 0.7). The gap between the reported and forecasted incidence for 2020 ranged from 5.1 to 5.7% (male 8.5%, 9.8%; female 2.3%, 3.5%). We estimated 1525-1596 missed cancer diagnoses (ARIMA estimate -98, 3148; AAPC 514, 1729) in 2020. Most missed diagnoses were in males (ARIMA 1361 [327, 2394]; AAPC 1401 [1353, 1460]), with an estimated 479-557 missed cases of colorectal cancer (ARIMA 112, 837; AAPC 518, 597) and 256-352 missed cases of prostate cancer (AAPC 231, 280; ARIMA 110, 594). CONCLUSION: The incidence of new cancer diagnoses declined in 2020 contrary to the long-term increase over the previous decades. Significantly lower diagnoses than expected were observed in males, particularly for colorectal and prostate cancers. Fewer reported cancer cases indicate missed diagnoses and could lead to delayed treatment that could impact future health outcomes.


Assuntos
COVID-19 , Neoplasias , Humanos , Masculino , Feminino , Hong Kong/epidemiologia , COVID-19/epidemiologia , Pandemias , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Previsões , Incidência
5.
Zhonghua Bing Li Xue Za Zhi ; 53(2): 162-167, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38281784

RESUMO

Objective: To investigate pathological features and differential diagnosis in the gonads with disorder of sex development. Methods: Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People's Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed. Results: Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT. Conclusions: Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.


Assuntos
Transtornos do Desenvolvimento Sexual , Gônadas , Humanos , Masculino , Feminino , Adolescente , Gônadas/patologia , Transtornos do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/patologia , Testículo/patologia , Ovário/patologia , Cariotipagem
7.
Hernia ; 28(1): 97-107, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37648895

RESUMO

PURPOSE: Literature on one- versus two-staged abdominal wall reconstruction (AWR) with complex gastrointestinal reconstruction (GIR) is limited to single-arm case series with a focus on patients who complete all planned stages. Herein, we describe our experience with both one- and two-staged approaches to AWR/GIR, with attention to those who did not complete both intended stages. METHODS: A retrospective review of prospectively collected data was conducted to identify patients who underwent a one- or two-stage approach to GIR/AWR from 2013 to 2020. The one-stage approach included GIR and definitive sublay mesh herniorrhaphy. The two-stage approach included Stage 1 (S1)-GIR and non-definitive herniorrhaphy and Stage 2 (S2)-definitive sublay mesh herniorrhaphy. RESULTS: Fifty-four patients underwent GIR/AWR: 20 (37.0%) underwent a planned 1-stage operation while 34 (63.0%) underwent S1 of a planned 2-stage approach. Patients assigned to the 2-stage approach were more likely to be smokers, have a history of mesh infection, have an enterocutaneous fistula, and a contaminated wound class (p<0.05). Of the 34 patients who underwent S1, 12 (35.3%) completed S2 during the mean follow-up period of 44 months while 22 (64.7%) did not complete S2. Of these, 10 (45.5%) developed hernia recurrence but did not undergo S2 secondary to elective nonoperative management (40%), pending preoperative optimization (30%), additional complex GIR (10%), hernia-related incarceration requiring emergent surgery (10%), or unrelated death (10%). No differences in outcome including SSI, SSO, readmission, and recurrence were noted between the 12 patients who completed the two-stage approach and the 20 patients who completed a one-stage approach, despite increased risk factors for complications in the 2-stage group (p>0.05). CONCLUSION: Planned two-stage operations for GIR/AWR may distribute operative complexity and post-operative morbidity into separate surgical interventions. However, many patients may never undergo the intended definitive S2 herniorrhaphy. Future evaluation of 1- versus 2-stage GIR/AWR is needed to clarify indications for each approach. This work must also consider the frequent deviations from intended clinical course demonstrated in this study.


Assuntos
Parede Abdominal , Abdominoplastia , Hérnia Ventral , Humanos , Parede Abdominal/cirurgia , Hérnia Ventral/cirurgia , Hérnia Ventral/etiologia , Herniorrafia/efeitos adversos , Resultado do Tratamento , Abdominoplastia/efeitos adversos
8.
Ecotoxicol Environ Saf ; 269: 115741, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38029584

RESUMO

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.


Assuntos
Desinfecção , Reprodução , Humanos , Feminino , Idoso , Desinfecção/métodos , Coagulação Sanguínea , Ácido Tricloroacético/urina , Biomarcadores/urina , Ácido Dicloroacético/urina
9.
Artigo em Chinês | MEDLINE | ID: mdl-37805769

RESUMO

Objective: To investigate the curative effects of bi-pedicled deep inferior epigastric perforator (DIEP) flap in repairing large soft tissue defects in the lower limbs. Methods: A retrospective observational study was conducted. From February 2016 to June 2020, 16 patients with large soft tissue defects in the lower limbs caused by trauma or after tumor/scar resection were admitted to the Department of Hand Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, including 9 males and 7 females, aged 25-58 years, with the area of soft tissue defects ranging from 14.0 cm×8.0 cm to 32.0 cm×18.0 cm. Using the abdomen as the donor site, the conjoined abdominal wall flap, i.e., the bi-pedicled DIEP flap (with an area ranging from 15.0 cm×9.0 cm to 32.0 cm×20.0 cm) carrying two sets of the trunk of the deep inferior epigastric artery was designed and resected to repair the wound. The donor site wound was sutured directly. The flap survival and wound healing in the donor and recipient areas were observed after operation. The curative effect was evaluated during the follow-up. At the last follow-up, the American Knee Society score and lower extremity functional scale were used to assess the functions of knee joint and lower limb, respectively. Results: The flaps of 15 patients survived after operation; the flap of one patient had partial infection at the edge after operation but healed after debridement and dressing change. The wounds in the donor and recipient areas of 16 patients all healed well. Follow-up of 16-28 months showed that the recipient area had a good shape and pliable texture, and there was no obvious swollen appearance, hyperpigmentation, or abnormal hair growth; the donor site had linear scar only, with no complications such as abdominal hernia or hyperplastic scar; the functions of knee joint and lower limb were well reconstructed, with no recurrence of tumor. At the last follow-up, among the 4 patients with knee joint injury, 3 cases were excellent and 1 case was good in the evaluation of knee joint function; among the 12 patients with lower limb injury, 9 cases were excellent and 3 cases were good in the evaluation of lower limb function. Conclusions: The donor site of bi-pedicled DIEP flap is concealed with abundant tissue and large area for resection, with which can be used to repair large soft tissue defects in the lower limbs, achieving good short-term results of appearance and function restoration.


Assuntos
Traumatismos do Joelho , Neoplasias , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Masculino , Feminino , Humanos , Transplante de Pele , Cicatriz/cirurgia , Lesões dos Tecidos Moles/cirurgia , Cicatrização , Extremidade Inferior , Resultado do Tratamento , Traumatismos do Joelho/cirurgia , Neoplasias/cirurgia
10.
Clin Radiol ; 78(12): e941-e949, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37788968

RESUMO

AIM: To investigate how magnetic resonance imaging (MRI) examinations are protocolled in tertiary paediatric neuroradiology centres around the UK for some of the more common presentations encountered in paediatric neuroradiology, and to identify any variations of note. MATERIALS AND METHODS: All 19 UK tertiary paediatric neuroradiology centres registered with the British Society of Neuroradiologists-Paediatric Group were contacted and asked if they could provide a copy of their standard MRI protocols. Twelve responded (63%) and 10 of the more common presentations were selected and the standard acquired sequences obtained at each participating centre were compared. Where available the collated protocols were also compared against current published guidance. RESULTS: The basic sequences carried out by centres around the UK are similar; however, there are lots of variations overall. The only standardised protocol currently being implemented nationally in paediatric imaging is that for brain tumours. Otherwise, chosen protocols are generally dependent on the preferences and technical capabilities of individual centres. Suggested published protocols also exist for non-accidental injury (NAI), multiple sclerosis, epilepsy, and head and neck imaging. CONCLUSIONS: The differences in MRI protocolling depend in part on technical capabilities and in part on the experience and preferences of the paediatric neuroradiologists at each centre. For most presentations, there is no consensus as to what constitutes the perfect protocol. The present results will be useful for specialist centres who may wish to review their current protocols, and for more generalist centres to use as a reference to guide their MRI protocolling.


Assuntos
Neoplasias Encefálicas , Hospitais Pediátricos , Criança , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Centros de Atenção Terciária , Reino Unido
12.
Pediatr Surg Int ; 39(1): 262, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668756

RESUMO

INTRODUCTION: Central venous catheter (CVC) placement is commonly performed in children. We aim to develop simple formulas to predict CVC intravascular length to minimise radiation exposure associated with the procedure. METHODS: 124 paediatric patients who received tunnelled neck CVCs and subsequent CT thorax at Hong Kong Children's Hospital from January 2020 to July 2022 were reviewed retrospectively. Formula development cohorts were subdivided by insertion sites-9 right external jugular vein (REJV), 41 right internal jugular vein (RIJV), 14 left external jugular vein (LEJV), 10 left internal jugular vein (LIJV). Using measurements from CT by two radiologists, formulas predicting the CVC intravascular length based on height and insertion sites were developed using a linear regression model. These formulas were tested with validation cohorts (10 randomly selected cases in REJV and RIJV groups respectively). Validation cohorts were not available for LEJV and LIJV groups due to small sample sizes. RESULT: The goodness-of-fit (R^2) of all formulas are above 0.8. In the validation cohorts, the REJV formula was predictive of intravascular CVC length within 1 cm in 70% of CVC with mean absolute difference of 0.63 cm (SD 0.48 cm), and the RIJV formula was predictive of intravascular CVC length within 1 cm in 80% of CVC with mean absolute difference of 0.67 cm (SD 0.53 cm). CONCLUSION: Intravascular CVC length can be estimated using simple formulas based on height and insertion sites. Further prospective validation of the LEJV and LIJV formulas is needed.


Assuntos
Cateteres Venosos Centrais , Humanos , Criança , Estudos Retrospectivos , Veias Braquiocefálicas , Hospitais Pediátricos , Veias Jugulares/diagnóstico por imagem
14.
Zhonghua Wai Ke Za Zhi ; 61(8): 727-732, 2023 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-37400216

RESUMO

Proximal tibial aspect ratio (PTAR) is closely related to age, disease status and cutting parameters with considerable inter-individual variation independent of gender and race, nevertheless the aspect ratio of tibial components from different manufacturers remains relatively constant from smallest to largest size. As a result, component mismatching is an unavoidable dilemma during tibia preparation in total knee arthroplasty (TKA). Various prosthesis systems all can achieve more than 80% coverage on proximal tibia, whereas their optimal fit rates are generally not more than 50%. It is difficult for symmetrical components to avoid anteroposterior mismatch, internal malrotation tends to occur when maximum coverage is pursued on the resected surface with a medial dominant plateau or lower PTAR. Although it is easier to achieve a balance of rotation and coverage with anatomical components, significant anteromedial overhang tends to appear on the resected surface with a symmetrical or lateral dominant plateau. Further researches should focus on the law of inter-individual variability of proximal tibial morphology, the quantitative definition of "ideal matching" safety zone of key morphological parameters on different areas of proximal tibia and the methodology of realizing"ideal matching"in the majority patients with the least amount of component sizes. In addition, with the rapid development of additive manufacturing and digital orthopedic technology, individual customized implant is expected to become a breakthrough point in the field of TKA component fitting.

15.
Artigo em Chinês | MEDLINE | ID: mdl-37248081

RESUMO

Objective: To understand the late reporting and the under-reporting of occupational disease from 2018 to 2020 in China and analyze the causes, so as to provide scientific evidence for improving the quality of occupational disease reports in China, timely acquiring the incidence of occupational disease, and assessing the occupational hazards. Methods: From May to December 2021, A total of 320 occupational disease diagnostic institutions were selected for investigation. The original documents of occupational disease diagnosis cases from 2018 to 2020 were compared with the online reported cases, and late reported and under-reported cases of occupational disease were analyzed. Results: A total of 32207 diagnosed cases from 2018 to 2020 were investigated, including 28934 confirmed cases and 3273 cases without occupational disease. The overall late reported rate and under-reported rate of confirmed cases were 20.2% and 2.1%, respectively. There were significant differences in the rate of late reporting and under-reporting of occupational diseases in different regions and different types of diagnostic institutions (P<0.001). The southwest region had the highest rates of late reporting and under-reporting, 61.6% and 7.9% respectively. The late reported rate of all kinds of occupational diseases was about 15.0%, and the under-reported rate was from 1.5.0% to 5.0%. Conclusion: At present, the phenomenon of late reporting and under-reporting occupational diseases is still obvious. It is necessary to strengthen the inspection of occupational disease reporting, improve the quality of occupational disease reporting, and provide scientific basis for the formulation of occupational disease prevention and control policies.


Assuntos
Doenças Profissionais , Humanos , Doenças Profissionais/epidemiologia , Doenças Profissionais/diagnóstico , China/epidemiologia , Incidência
16.
Artigo em Chinês | MEDLINE | ID: mdl-37248088

RESUMO

The surveillance of occupational disease has entered a new stage ofdevelopment, with the implementation of the national health informatization project. To improve the efficiency and quality of occupational disease monitoring information reporting in this paper, the system architecture and related management regulations, as long as the major changes and achievement of "surveillance system of occupational disease and health hazards information" under the framework of National Health Insurance Informatization Project were elaborated. The deficiencies existing in the system were analyzed, and expectation for the construction of the occupational disease surveillance system was addressed.


Assuntos
Doenças Profissionais , Saúde Ocupacional , Humanos
17.
Artigo em Chinês | MEDLINE | ID: mdl-36882283

RESUMO

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is an endogenous short peptide produced through the continuous hydrolysis of Thymosin ß4 by meprin-α and prolyl oligopeptidase. It has the functions of immune regulation, promoting angiogenesis, tumorigenesis and anti-fibrosis in organs. In this paper, according to some our research results and related literatures in recent years, a review of Ac-SDKP research progress was written.


Assuntos
Transformação Celular Neoplásica , Oligopeptídeos , Humanos
18.
Clin Oncol (R Coll Radiol) ; 35(4): 262-268, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737311

RESUMO

AIMS: To report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. MATERIALS AND METHODS: In 2003-2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan-Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. RESULTS: Of 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3-7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. CONCLUSION: In low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.


Assuntos
Braquiterapia , Neoplasias da Próstata , Humanos , Masculino , Pessoa de Meia-Idade , Braquiterapia/métodos , Estudos Prospectivos , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Dosagem Radioterapêutica
19.
Aliment Pharmacol Ther ; 57(8): 872-885, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36670060

RESUMO

BACKGROUND: Dysregulated bile acid (BA) metabolism has been linked to steatosis, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD). AIM: To determine whether circulating BA levels accurately stage liver fibrosis in NAFLD. METHODS: We recruited 550 Chinese adults with biopsy-proven NAFLD and varying levels of fibrosis. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs. RESULTS: Compared to those without fibrosis, patients with mild fibrosis (stage F1) had significantly higher levels of secondary BAs, and increased diastolic blood pressure (DBP), alanine aminotransferase (ALT), body mass index, and waist circumstance (WC). The combination of serum BAs with WC, DBP, ALT, or Homeostatic Model Assessment for Insulin Resistance performed well in identifying mild fibrosis, in men and women, and in those with/without obesity, with AUROCs 0.80, 0.88, 0.75 and 0.78 in the training set (n = 385), and 0.69, 0.80, 0.61 and 0.69 in the testing set (n = 165), respectively. In comparison, the combination of BAs and clinical/biochemical biomarkers performed less well in identifying significant fibrosis (F2-4). In women and in non-obese subjects, AUROCs were 0.75 and 0.71 in the training set, 0.65 and 0.66 in the validation set, respectively. However, these AUROCs were higher than those observed for the fibrosis-4 index, NAFLD fibrosis score, and Hepamet fibrosis score. CONCLUSIONS: Secondary BA levels were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum BAs and clinical/biochemical biomarkers for identifying mild fibrosis merits further assessment.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Masculino , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Ácidos e Sais Biliares , Cirrose Hepática/complicações , Inflamação/complicações , Biomarcadores , Obesidade/complicações , Fígado/patologia
20.
J Cancer Res Clin Oncol ; 149(9): 5907-5914, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36595042

RESUMO

BACKGROUND: Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin® has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with Avastin® sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer (nsNSCLC). METHOD: In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received TAB008 or Avastin® 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or Avastin® 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression-free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady-state pharmacokinetics. RESULTS: A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin® group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin®, and the ORR ratio was 1 (90% CI 0.89-1.14), well within the predefined equivalence margin of 0.75-1.33. No significant differences were found in DCR within 6 cycles (95.703% vs 95.367%, p = 0.8536), DoR (8.17 vs 7.3 months, p = 0.3526), PFS (9.10 vs. 7.97 months, p = 0.9457), 1 year overall survival rate (66.2% vs 68%, p = 0.6793), or OS (20.4 vs 17.6 months, p = 0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin® group. Anti-drug antibodies were reported in 3 of 277 (1.08%) TAB008 patients, and 5 of 271 (1.85%) Avastin® patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin®, which became negative upon follow-up. The steady-state trough concentrations (Cssmin) were 106.13 µg/mL in TAB008 group and 96.03 µg/mL in Avastin® groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00-125.00% (90% CI was 101.74-120.05%). CONCLUSIONS: TAB008 is similar to Avastin® in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov number; NCT05427305.


Assuntos
Medicamentos Biossimilares , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Bevacizumab , Neoplasias Pulmonares/patologia , Medicamentos Biossimilares/farmacocinética , Fator A de Crescimento do Endotélio Vascular , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel , Receptores ErbB , Método Duplo-Cego
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