Journal of the Chinese Medical Association最新文献

Background: Cell-free DNA (cfDNA) as an oncological biomarker has drawn much attention in recent years, but very limited effort has been made to investigate the prognostic values of cfDNA in distal common bile duct (CBD) cancer.

Methods: Plasma cfDNA was measured in 67 patients with resectable distal CBD cancer. Survival outcomes and the correlation of cfDNA with other conventional prognostic factors were determined.

Results: cfDNA levels were significantly higher in female patients, and those with poor tumor differentiation, abnormal serum carcinoembryonic antigen (CEA) level, and stage III cancer. The significant prognostic factors included a high cfDNA level (>8955 copies/mL), abnormal serum CEA level, stage III cancer, and positive resection margins. Compared with patients with high cfDNA level, those with lower cfDNA level (≤8955 copies/mL) had significantly better overall survival outcomes (74.4% vs 100% and 19.2% vs 52.6%, for 1- and 5-year survival rates, respectively, p = 0.001). The cfDNA level, perineural invasion, CEA level, and radicality were identified as independent prognostic factors for distal CBD cancer after multivariate analysis.

Conclusion: Circulating cfDNA levels play a significant role in predicting the prognosis and survival outcome for resectable distal CBD cancer. Furthermore, acting as a promising liquid biopsy, cfDNA could serve as a prognostic and predictive biomarker in combination with current conventional markers to improve diagnostic and prognostic efficacy.

Background: Thionamide-induced agranulocytosis (TiA) is a rare adverse event with a reported incidence of approximately 0.1% to 1.75%. Prompt recognition of TiA is critical to reduce the mortality rate. However, the differential diagnosis between cases of TiA and non-TiA neutropenia can be challenging due to the potential simultaneous involvement of other causes of neutropenia, such as concomitant chemotherapy, liver dysfunction, or infection. The aim of the present study was to investigate the possible factors associated with the development of TiA.

Methods: This was a retrospective cohort study of patients treated with antithyroid drugs (ATDs) in Taipei Veterans General Hospital, Taipei, Taiwan, from 2006 to 2018. Patients who developed a neutropenic event during treatment with ATDs were identified from their medical records. The diagnosis of TiA was based on the following: (1) development of neutropenia during treatment or within 7 days after previous exposure to the same ATDs; (2) complete resolution of neutropenia within 1 month after discontinuation of the culprit drug with an absolute neutrophil count (ANC) >1500/μL; and (3) exclusion of other causes of neutropenia. The incidence and risk factors of TiA were analyzed and compared with those of non-TiA neutropenia.

Results: Among 6644 patients treated with ATDs, 66 (mean age: 53 ± 15 years; 16.2% men) developed a neutropenic event and 20 were diagnosed with TiA (incidence: 0.3%). In the univariate analysis, compared with non-TiA neutropenia, TiA was associated with a lower Charlson Comorbidity Index, shorter treatment duration, lower cumulative ATD dosage, higher ATD dosage, higher ANC, and higher levels of free T4 at the time of the neutropenic event. In the multivariate logistic regression analysis, after adjusting for age, gender and the time to neutropenia, the cumulative ATD dose to neutropenia and ATD dosage at the time of the neutropenic event, Charlson Comorbidity Index, free T4 levels (odds ratio [OR], 4.44; 95% CI, 1.48-13.25), and ANC (OR, 1.00; 95% CI, 1.00-1.01) remained independently associated with TiA.

Conclusion: Patients with TiA were more likely to have higher levels of free T4 and ANC at the time of the neutropenic event vs those with non-TiA neutropenia.

Background: Cochlear implantation (CI) has long been the standard of care for patients with severe-to-profound hearing impairment. Yet the benefits of CI extend far beyond speech understanding, with mounting recent literature supporting its role in tinnitus abatement. However, those studies have uniformly analyzed the effects of tinnitus after the traditional 3-4 weeks waiting period between CI surgery and device activation. As many clinics are shifting these waiting intervals to become shorter (in some cases within 24 hours, little is known about tinnitus abatement very early in the postoperative period. The aim of this study was to compare preoperative and postoperative tinnitus handicaps in this unique but growing population of very early-activated patients.

Methods: Twenty-seven adults with severe-to-profound hearing impairment with chronic tinnitus (>6 months) were included. Patients with concomitant psychiatric disorders were excluded. All patients were implanted with the same array and were switched on within 24 hours after the surgery. Tinnitus Handicap Inventory (THI) was recorded preoperatively, immediately after activation at 24 hours postoperatively, at 1 week, 2 weeks, and I month after activation. Wilcoxon signed-rank test was used to compare values between preoperative assessment and respective fitting sessions.

Results: Mean THI 24 hours after implantation increased in comparison to that assessed preoperatively (77.6 vs 72.5, p = 0.001). By 1 week after surgery, the THI had decreased to 54.9 ( p < 0.001). This trend continued and was statistically significant at 2 weeks (36.0, p < 0.001) and 1 month (28.5, p < 0.001).

Conclusion: On average, most patients with tinnitus will note a significant improvement in their tinnitus handicap when activated within 24 hours of CI. However, tinnitus does increase between surgery and 24 hours, most likely reflecting not only intracochlear changes, but modulation of the entire auditory pathway. Following this early rise, the tinnitus continues to abate over the following month. Patients with tinnitus may benefit from early activation, although should be counseled that they may experience an exacerbation during the very early postoperative period.

Background: Aberrant glycosylation performed by glycosyltransferases is a leading cause of gastric cancer (GC). Protein O-fucosyltransferase 1 (POFUT1) expression is increased in GC specimens and cells. In this study, the biological effects and mechanisms of POFUT1 underlying the development of GC were investigated.

Methods: POFUT1 downregulated and upregulated GC cells were established. The effects of POFUT1 on cell proliferation, metastasis and apoptosis were examined using cell counting kit-8 (CCK8) assay, transwell assay, and flow cytometry. Subcutaneous xenograft tumor models were established followed by immunohistochemistry staining of resected tumors. Facilitating modulators and transcription factors were detected by western blot, immunofluorescence, luciferase reporter assay, and co-immunoprecipitation.

Results: POFUT1 played a pro-oncogenic role both in vivo and in vitro, which promoted proliferation and metastasis, as well as inhibited apoptosis in GC cells. POFUT1 promoted Cyclin D3 expression and inhibited the expression of apoptotic proteins, such as Bcl-2-associated X protein (Bax) and cleaved caspase 3, facilitating tumor growth. Moreover, POFUT1 accelerated matrix metalloproteases expression and attenuated E-cadherin expression, contributing to GC metastasis. In addition, POFUT1 expression promoted the expression and nuclear translocation of Notch1 intracellular domain (NICD1) and β-catenin and inhibited β-catenin phosphorylation degradation, accompanied by the activation of recombination signal binding protein-Jκ (RBP-J) and T-cell factor (TCF) transcription factors, respectively. It is notable that parafibromin integrated NICD1 and β-catenin, enabling the concerted activation of Wnt and Notch signaling targeted proteins.

Conclusion: These observations indicated that POFUT1 promoted GC development through activation of Notch and Wnt signaling pathways, which depended on the parafibromin-NICD1-β-catenin complex. This work provides new evidence for the further diagnosis and treatment of GC.

Background: The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan.

Methods: Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models.

Results: The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT 12 ) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT 12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m 2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047).

Conclusion: Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies.

Background: ChAdOx1 nCoV-19 vaccine has been widely used. Some unexpected adverse effects such as the development of systemic hyper inflammation with multiorgan involvement after vaccination, in rare cases, have been reported. However, its pathogenesis remains unclear.

Methods: This study recruited two cases who suffered from systemic inflammation following ChAdOx1 nCoV-19 vaccine and two 30-year-old male volunteers without underlying disease who have received ChAdOx1 nCoV-19 vaccine as control group. Blood samples were collected from our patients and healthy subjects before and after treatment with anti-inflammatory agent such as glucocorticoid and tocilizumab. The immune profile from our patients and healthy controls were measured using a human XL cytokine Proteome Profiler array (ARY022b, R&D Systems).

Results: Biochemical parameters revealed leukocytosis with segmented neutrophil dominance and elevated serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate, and ferritin in these two patients. The cytokine array revealed that mean levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3) (3640.3 vs 1580.5 pixels per inch [ppi]), B-cell activating factor (BAFF) (3036.8 vs 1471.0 ppi), urokinase plasminogen activator surface receptor (uPAR) (1043.1 vs 516.8 ppi), Resistin (1783.7 vs 711.3 ppi), platelet-derived growth factor (PDGF)-AB/BB (1980.7 vs 939.7 ppi), macrophage inflammatory protein-3-beta (MIP-3β) (911.9 vs 346.2 ppi), and interferon-inducible T-cell alpha chemoattractant (I-TAC) (1026.3 vs 419.7 ppi) were 2-fold higher in the patients than in normal subjects who received ChAdOx1 nCoV-19 vaccine.

Conclusion: We demonstrated that systemic inflammation may occur in subjects who have received the ChAdOx1 nCoV-19 vaccination. Moreover, we proposed immune markers, which may be implicated in the pathogenesis of systemic inflammation following COVID-19 vaccination as potential diagnostic biomarkers.

Background: Remote reporting is an important preventive measure against coronavirus disease 2019 (COVID-19) for radiology departments; it reduces the chance of cross-infections between coworkers. The purpose of this study was to evaluate how the preferred locations that radiologists filed reports from changed in response to COVID-19 by measuring the use of internal teleradiology workstations.

Methods: Data were obtained from the radiological information system (RIS) database at our institution, which recorded the reporting workstation for each radiological examination. The reporting activities in 2021 were divided into computed radiography (CR) and computed tomography (CT)/magnetic resonance imaging (MRI) groups. The Wilcoxon signed-rank test was used to measure differences in the use of off-site workstations in prepandemic, midpandemic, and postpandemic periods.

Results: There were statistically significant increases in the number of reports filed from off-site workstations for each attending physician from the prepandemic period to the midpandemic period in both the CR (15.1%-25.4%, p = 0.041) and CT/MRI (18.9%-28.7%, p = 0.006) groups. There was no significant difference noted between the prepandemic and postpandemic periods for either the CR (15.1% vs 18.4%, p = 0.727) or CT/MRI group (18.9% vs 23.3%, p = 0.236).

Conclusion: In response to the COVID-19 outbreak, radiologists used internal teleradiology to report CR and CT/MRI examinations significantly more frequently. In contrast to the predictions of previous studies, the use of internal teleradiology returned to baseline levels after the pandemic was under control.