1.Cost-effectiveness Analysis of Adebrelimab Combined with Chemotherapy in First Line Treatment of Extensive Stage Small-cell Lung Cancer
Yue LI ; Shujia KONG ; Pin ZHAO ; Xuemei WANG ; Liju LIANG ; Zhiying WENG
Chinese Journal of Modern Applied Pharmacy 2024;41(9):1267-1274
OBJECTIVE
To evaluate the cost-effectiveness of adebrelimab combined with chemotherapy versus chemotherapy alone in the first-line treatment of extensive stage small cell lung cancer from Chinese healthcare system perspective.
METHODS
Using the data obtained from the CAPSTONE-1 trial(230 cases for adebrelimab group, and 232 cases for chemotherapy group), Markov model was created for simulation of the disease development process of the extensive stage small cell lung cancer. The total costs, quality-adjusted life-years(QALYs) and incremental cost-effectiveness ratio(ICER) in each group were calculated. The sensitivity of key parameters was analyzed.
RESULTS
Compared with pure chemotherapy(etoposide plus carboplatin chemotherapy), the ICER of adebrelimab combined with chemotherapy was 157128.79 yuan·QALY−1 under the situation of charity assistance, and 351367.27 yuan·QALY −1 in the environment of no charity assistance. Sensitivity analysis showed that the utility and the cost of adebrelimab were the main influence parameter.
CONCLUSION
Adebrelimab combined with chemotherapy regimen has no cost-effective advantage versus chemotherapy alone in the treatment of extensive stage small cell lung cancer under the current economic level of China; the probability of adebrelimab combined with chemotherapy being cost- effectiveness was 44.5% under the situation of charity assistan.
2.The Chinese guideline for management of snakebites
Lai RONGDE ; Yan SHIJIAO ; Wang SHIJUN ; Yang SHUQING ; Yan ZHANGREN ; Lan PIN ; Wang YONGGAO ; Li QI ; Wang JINLONG ; Wang WEI ; Ma YUEFENG ; Liang ZIJING ; Zhang JIANFENG ; Zhou NING ; Han XIAOTONG ; Zhang XINCHAO ; Zhang MAO ; Zhao XIAODONG ; Zhang GUOQIANG ; Zhu HUADONG ; Yu XUEZHONG ; Lyu CHUANZHU
World Journal of Emergency Medicine 2024;15(5):333-355
In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.
3.Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study
Shuqin ZHANG ; Zhouqiao WU ; Bowen HUO ; Huining XU ; Kang ZHAO ; Changqing JING ; Fenglin LIU ; Jiang YU ; Zhengrong LI ; Jian ZHANG ; Lu ZANG ; Hankun HAO ; Chaohui ZHENG ; Yong LI ; Lin FAN ; Hua HUANG ; Pin LIANG ; Bin WU ; Jiaming ZHU ; Zhaojian NIU ; Linghua ZHU ; Wu SONG ; Jun YOU ; Su YAN ; Ziyu LI
Chinese Journal of Gastrointestinal Surgery 2024;27(3):247-260
Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.
4.Short-term outcomes of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted gastrectomy for gastric cancer: a retrospective cohort study
Yichuan FAN ; Chi ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of Gastrointestinal Surgery 2024;27(8):808-815
Objective:To compare and analyze the short-term efficacy of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted radical gastrectomy for gastric cancer.Method:In this retrospective cohort study, clinical pathological data of 190 patients with gastric cancer were collected from the clinical database of the First Affiliated Hospital of Dalian Medical University from 2020 Dec to 2023 May. The cohort comprised 136 men and 54 women aged 65 (30–85) years. Ninety of these patients had undergone robot assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the robot-assisted group. The remaining 100 patients had undergone laparoscopic- assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the laparoscopic control group. Variables investigated included surgical and postoperative factors and postoperative complications.Result:The procedure was successfully completed without the need to transition to open surgery in every patient in both groups. The median duration of surgery was 315 (270, 360) minutes and 240 (202, 280) minutes, median intraoperative blood loss 20 (10, 30) mL and 30 (10, 50) mL, median incision length 12.0 (10.8,13.0) cm and 10.0 (8.0, 10.8) cm, median time to first postoperative passage of flatus 4 (3, 5) days and 4 (4, 5) days, median time to first postoperative fluid intake 6 (4, 7) days and 8 (6, 9) days, time to gastric tube removal 4 (3, 7) days and 6 (5, 8) days, median time to drainage tube removal 8 (7, 10) days and 10 (9, 12) days, median duration of postoperative hospitalization 8 (7, 11) days and 12 (10, 14) days, and cost of surgery (7.6±1.2)×10 4 yuan and (4.0±0.6)×10 4 yuan in the robot-assisted and laparoscopic control groups, respectively. All the differences in the above indicators between the two groups of patients were statistically significant (all P<0.05). There were also significantly fewer complications in the robot-assisted than the laparoscopic control group (28.9% [26/90] vs. 44.0% [44/100], χ 2=0.31, P=0.031). Further subgroup analysis showed that the following factors were associated with greater improvement in the robot-assisted than laparoscopic control group: male sex (OR=0.41, 95%CI: 0.20–0.83, P=0.015), body mass index Conclusion:The Da Vinci robotic surgical system is safe and feasible for gastrectomy achieving a shorter recover period and fewer preoperative comorbidities.
5.Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study
Shuqin ZHANG ; Zhouqiao WU ; Bowen HUO ; Huining XU ; Kang ZHAO ; Changqing JING ; Fenglin LIU ; Jiang YU ; Zhengrong LI ; Jian ZHANG ; Lu ZANG ; Hankun HAO ; Chaohui ZHENG ; Yong LI ; Lin FAN ; Hua HUANG ; Pin LIANG ; Bin WU ; Jiaming ZHU ; Zhaojian NIU ; Linghua ZHU ; Wu SONG ; Jun YOU ; Su YAN ; Ziyu LI
Chinese Journal of Gastrointestinal Surgery 2024;27(3):247-260
Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.
6.Short-term outcomes of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted gastrectomy for gastric cancer: a retrospective cohort study
Yichuan FAN ; Chi ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of Gastrointestinal Surgery 2024;27(8):808-815
Objective:To compare and analyze the short-term efficacy of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted radical gastrectomy for gastric cancer.Method:In this retrospective cohort study, clinical pathological data of 190 patients with gastric cancer were collected from the clinical database of the First Affiliated Hospital of Dalian Medical University from 2020 Dec to 2023 May. The cohort comprised 136 men and 54 women aged 65 (30–85) years. Ninety of these patients had undergone robot assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the robot-assisted group. The remaining 100 patients had undergone laparoscopic- assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the laparoscopic control group. Variables investigated included surgical and postoperative factors and postoperative complications.Result:The procedure was successfully completed without the need to transition to open surgery in every patient in both groups. The median duration of surgery was 315 (270, 360) minutes and 240 (202, 280) minutes, median intraoperative blood loss 20 (10, 30) mL and 30 (10, 50) mL, median incision length 12.0 (10.8,13.0) cm and 10.0 (8.0, 10.8) cm, median time to first postoperative passage of flatus 4 (3, 5) days and 4 (4, 5) days, median time to first postoperative fluid intake 6 (4, 7) days and 8 (6, 9) days, time to gastric tube removal 4 (3, 7) days and 6 (5, 8) days, median time to drainage tube removal 8 (7, 10) days and 10 (9, 12) days, median duration of postoperative hospitalization 8 (7, 11) days and 12 (10, 14) days, and cost of surgery (7.6±1.2)×10 4 yuan and (4.0±0.6)×10 4 yuan in the robot-assisted and laparoscopic control groups, respectively. All the differences in the above indicators between the two groups of patients were statistically significant (all P<0.05). There were also significantly fewer complications in the robot-assisted than the laparoscopic control group (28.9% [26/90] vs. 44.0% [44/100], χ 2=0.31, P=0.031). Further subgroup analysis showed that the following factors were associated with greater improvement in the robot-assisted than laparoscopic control group: male sex (OR=0.41, 95%CI: 0.20–0.83, P=0.015), body mass index Conclusion:The Da Vinci robotic surgical system is safe and feasible for gastrectomy achieving a shorter recover period and fewer preoperative comorbidities.
7.ZnO Quantum Dot and SnO2 Quantum Dot Labeling Antibodies and Single Particle Inductively Coupled Plasma Mass Spectrometry Coupled with Magnetic Immunoassay for Detection of Ovarian Cancer Biomarkers CA125 and HE4 in Human Serum
Yu-Pin CAO ; Hai-Ping CHEN ; Jie LIANG ; Bi-Yang DENG
Chinese Journal of Analytical Chemistry 2024;52(10):1562-1572
Ovarian cancer is one of the most fatal of all the gynecological malignancies.The detection of biomarker is one of the diagnostic bases for the disease.The combined detection of carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)in human serum can improve the accuracy of clinical diagnosis for ovarian cancer.In this study,a new method for analysis of ovarian cancer biomarkers CA125 and HE4 in human serum using zinc oxide quantum dot(ZnO QD)and tin oxide quantum dot(SnO2 QD)labeled antibodies coupled with single particle inductively coupled plasma mass spectrometry(ICP-MS)was developed.CA125 and HE4 antigens were captured by amino-modified magnetic nanoparticles combined with CA125 and HE4 primary antibodies.CA125 and HE4 secondary antibodies were labeled by ZnO QD and SnO2 QD,respectively.The signal frequency of Zn and Sn was determined by ICP-MS to realize the quantitative analysis of CA125 and HE4.The linear detection ranges of CA125 and HE4 were 0.02-200 U/mL and 0.02-100 ng/mL,the detection limits were 0.004 U/mL and 0.006 ng/mL(3σ),and the RSDs were 2.2%and 3.5%(n=6),respectively.This method had many advantages such as high sensitivity,good selectivity and less reagent consumption,and was successfully applied to determine the content of CA125 and HE4 in human serum.
8.Clinical efficacy of da Vinci Xi robotic surgical system assisted pylorus and vagus preser-ving partial gastrectomy for early gastric cancer
Yichuan FAN ; Chi ZHANG ; Maohua WEI ; Hua ZHONG ; Haitao DUAN ; Weifeng SUN ; Liang CAO ; Jian ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of Digestive Surgery 2023;22(8):1014-1020
Objective:To investigate the clinical efficacy of da Vinci Xi robotic surgical system assisted pylorus and vagus preserving partial gastrectomy (RaPPG) for early gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 40 patients with early gastric cancer who were admitted to the First Affiliated Hospital of Dalian Medical University from December 2020 to November 2022 were collected. There were 26 males and 14 females, aged (64±8)years. Of the 40 patients, 19 patients undergoing da Vinci Xi RaPPG were divided into the robotic assisted group, and 21 patients undergoing laparoscopic assisted pylorus and vagus preserving partial gastrectomy (PPG) were divided into the laparoscopic control group. Observation indicators: (1) surgical situations; (2) postoperative complications; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Surgical situations. All patients in the two groups underwent surgery successfully, without conversion to laparotomy. The operation time, volume of intraoperative blood loss, time to postoperative first flatus, time to postoperative first liquid food intake, time to post-operative drainage tube removal, duration of postoperative hospital stay, tumor diameter, distance from distal resection margin to tumor were (298±52)minutes, 10(10, 10)mL, 3.0(3.0, 3.0)days, 3.0(3.0,4.0)days, 6.0(6.0,8.0)days, 7.0(6.0,8.0)days, (2.3±0.7)cm, 3.0(2.0,3.0)cm in patients of the robotic assisted group, versus (236±37)minutes, 25(15,50)mL, 5.0(4.0,5.0)days, 6.0(5.5,7.0)days, 8.0(8.0,9.5)days, 8.0(7.5,9.5)days, (2.9±1.1)cm ,2.0(1.5,2.0)cm in patients of the laparoscopic control group, showing significant differences in the above indicators between the two groups ( t=4.41, Z=-3.38, -4.75, -4.38, -2.98, -2.58, t=-2.10, Z=-3.03, P<0.05). (2) Postoperative complications. Cases with postoperative complications, cases with delayed gastric emptying, cases with acid regurgita-tion, cases with atelectasis, cases with infection of incision, cases with hyperamylasemia, cases with uroschesis were 6, 1, 1, 0, 1, 3, 0 in patients of the robotic assisted group. The above indicators were 20, 4, 3, 2, 1, 9, 1 in patients of the laparoscopic control group. There was a significant difference in the postoperative complications between the two groups ( χ2=17.77, P<0.05). (3) Follow-up. Of the 40 patients, 34 patients were followed up. There were 16 patients in the robotic assisted group who were followed up for 9(range, 6-18)months, and there were 18 patients in the laparoscopic control group who were followed up for 16(range, 9-23)months. During the follow-up period, all patients had good anastomosis healing, pyloric contraction function, and gastric emptying function. Conclusions:da Vinci Xi RaPPG is safe and feasible for the treatment of early gastric cancer. Compared with laparoscopic assisted PPG, treatment of gastric cancer with da Vinci Xi RaPPG can significantly reduce the volume of intraoperative blood loss, shorten the time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative drainage tube removal, duration of postoperative hospital stay, benefit the distance from distal resection margin to tumor, and reduce the incidence of postoperative complications.
9.Efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma
Linhuan LI ; Zheng SONG ; Fen ZHOU ; Bingzhang TIAN ; Fangming WANG ; Jun WANG ; Pin LYU ; Gang LIANG ; Ye OU
Chinese Journal of Hepatobiliary Surgery 2023;29(1):38-42
Objective:To study the efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma.Methods:The clinical data of 58 patients with recurrent hepatocellular carcinoma who underwent surgical treatment from January 2010 to January 2018 at Hunan Provincial People’s Hospital were retrospectively analyzed. There were 50 males and 8 females, ranging in age from 28 to 78 (53.0±10.8) years old. Patients were divided into laparoscopic group ( n=27) and laparotomy group ( n=31) according to different surgical procedures. The differences in operative time, intraoperative blood loss, hospital stay, postoperative anal exhaustion time, postoperative complications and prognosis between the two groups were compared. Results:The intraoperative blood loss of laparoscopy group and laparotomy group were 100.0(50.0, 400.0) ml vs 300.0(100.0, 500.0) ml, the postoperative anal exhaustion time were (2.7±0.6) d vs (3.3±0.6) d, the hospital stay were (14.8±3.8) d vs (21.4±6.3) d, and these differences were statistically significant (all P<0.05). The operative time of the two groups were (243.4±27.2) min vs (217.5±34.7) min, with no statistical significance ( t=0.59, P=0.344). There were no significant differences between the two groups in postoperative complications (bile leakage, abdominal infection, hemorrhage, pleural effusion and hepatic encephalopathy) (all P>0.05); thetumor free survival, 1-year, and 3-year overall survival rates of the two groups were also not significantly different (both P>0.05). Conclusion:Laparoscopic surgery is safe and effective in the treatment of recurrent hepatocellular carcinoma, and its prognosis is similar to laparotomy, its complications are not significantly increased, which is worthy of promotion in clinic.
10.Clinical Characteristics, Genetic Features, and Long-Term Outcome of Wilson’s Disease in a Taiwanese Population: An 11-Year Follow-Up Study
Sung-Pin FAN ; Yih-Chih KUO ; Ni-Chung LEE ; Yin-Hsiu CHIEN ; Wuh-Liang HWU ; Yu-Hsuan HUANG ; Han-I LIN ; Tai-Chung TSENG ; Tung-Hung SU ; Shiou-Ru TZENG ; Chien-Ting HSU ; Huey-Ling CHEN ; Chin-Hsien LIN ; Yen-Hsuan NI
Journal of Movement Disorders 2023;16(2):168-179
Objective:
aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort.
Methods:
aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes.
Results:
aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations.
Conclusion
aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.


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