2.A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children
Li SONG ; Ling JIN ; Yonghong ZHANG ; Xiaomei YANG ; Yanlong DUAN ; Mincui ZHENG ; Xiaowen ZHAI ; Ying LIU ; Wei LIU ; Ansheng LIU ; Xiaojun YUAN ; Yunpeng DAI ; Leping ZHANG ; Jian WANG ; Lirong SUN ; Rong LIU ; Baoxi ZHANG ; Lian JIANG ; Huixia WEI ; Kailan CHEN ; Runming JIN ; Xige WANG ; Haixia ZHOU ; Hongmei WANG ; Shushuan ZHUANG ; Chunju ZHOU ; Zifen GAO ; Xiao MU ; Kaihui ZHANG ; Fu LI
Chinese Journal of Pediatrics 2024;62(10):941-948
Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.
3.Efficacy and safety of Omalizumab for the treatment of pediatric allergic asthma: a retrospective multicenter real-world study in China
Li XIANG ; Baoping XU ; Huijie HUANG ; Mian WEI ; Dehui CHEN ; Yingying ZHAI ; Yingju ZHANG ; Dan LIANG ; Chunhui HE ; Wei HOU ; Yang ZHANG ; Zhimin CHEN ; Jingling LIU ; Changshan LIU ; Xueyan WANG ; Shan HUA ; Ning ZHANG ; Ming LI ; Quan ZHANG ; Leping YE ; Wei DING ; Wei ZHOU ; Ling LIU ; Ling WANG ; Yingyu QUAN ; Yanping CHEN ; Yanni MENG ; Qiusheng GE ; Qi ZHANG ; Jie CHEN ; Guilan WANG ; Dongming HUANG ; Yong YIN ; Mingyu TANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(1):64-71
Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.
4.Analysis of drug resistance gene in Mycoplasma pneumoniae and 13 pathogens in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia
Dawei SHI ; Ling LIU ; Mengmeng ZHAO ; Leping YE ; Wei ZHOU ; Dongxing GUO ; Dan LI ; Haiwei DOU ; Peng TU ; Ruijie WAN ; Deli XIN
Chinese Journal of Applied Clinical Pediatrics 2022;37(12):893-896
Objective:To investigate drug resistance gene in Mycoplasma pneumoniae(MP) and the distribution of 13 respiratory pathogens in bronchoalveolar lavage fluid(BALF) of children with Mycoplasma pneumoniae pneumonia(MPP).Methods:A total of 100 BALF of children with MPP in Peking University Third Hospital and Peking University First Hospital from January 2018 to January 2019 were collected.Fluorogenic quantitative PCR was used to detect nucleic acid and it′s drug resistance gene of MP and multiple PCR method was adopted to detect influenza A virus, influenza A virus-H 1N 1, influenza A virus-H 3N 2, influenza B, human parainfluenza virus, adenovirus, human bocavirus, human rhinovirus, Chlamydia pneumoniae, human metapneumovirus, MP, human coronavirus, and respi-ratory syncytial virus gene, and the results were compared by using Chi square test. Results:In 100 BALF samples, MP and drug resistance gene were detected by fluorogenic quantitative PCR.Totally, 83 cases (83.00%) were MP positive and 78 cases (93.98%) were drug resistant.All of them had the point mutations A2063G in V region of 23S rRNA domain.A total of 13 kinds of respiratory pathogens were detected by multiplex PCR method, and 89 cases (89.00%) were positive.Totally, 79 cases (79.00%) were MP positive, of which 74 cases (74.00%) detected only MP, and 5 cases (5.00%) detected MP combined with other pathogens.Other pathogens were detected in 10 cases (10.00%). The virus detection rate of 0-4 years old group was higher than that of >4-6 years old group ( P=0.042) and >6 years old group ( P=0.002), and the differences were statistically significant. Conclusions:MP can be detected in most BALF samples of MPP children, the drug resistance phenomenon is serious, and the main point mutation is A2063G.There were other respiratory pathogens and 2 or 3 pathogens were detected in a small number of BALF samples.
5.Expert consensus on the diagnosis, treatment and prevention of monkeypox in children
Rongmeng JIANG ; Yuejie ZHENG ; Lei ZHOU ; Luzhao FENG ; Lin MA ; Baoping XU ; Hongmei XU ; Wei LIU ; Zhengde XIE ; Jikui DENG ; Lijuan XIONG ; Wanjun LUO ; Zhisheng LIU ; Sainan SHU ; Jianshe WANG ; Yi JIANG ; Yunxiao SHANG ; Miao LIU ; Liwei GAO ; Zhuang WEI ; Guanghua LIU ; Gang LIU ; Wei XIANG ; Yuxia CUI ; Gen LU ; Min LU ; Xiaoxia LU ; Runming JIN ; Yan BAI ; Leping YE ; Dongchi ZHAO ; Adong SHEN ; Xiang MA ; Qinghua LU ; Fengxia XUE ; Jianbo SHAO ; Tianyou WANG ; Zhengyan ZHAO ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(13):964-973
Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.
6.LncRNA C21orF96 promotes the invasion and metastasis of gastric cancer by regulating the expression of miR-875-5p and USF2 genes
Shicheng ZHOU ; Qinhui SUN ; Hongxia ZHANG ; Guodong LIAN ; Hongjun LIU ; Leping LI ; Xiaobo GUO
Chinese Journal of General Surgery 2020;35(1):57-60
Objective To verify that lncRNA-C21orF96 regulates the expression of miRNA-875-5p and USF2 genes and promotes the invasion and metastasis of gastric cancer.Methods RT-PCR was used to measure the expression of lncRNA-C21orF96 related miRNA in gastric cancer cells.pcDNA3.1 plasmid was used to over-express lncRNA-C21orF96 in KATO-Ⅲ and siRNA was used to knockdown the expression of lncRNA-C21orF96 in SGC-7901,and RT-PCR was used to measure the expression of miRNA-875-5p and USF2 genes;By overexpressing lncRNA-C21orF96 in MKN45,transwell was used to observe changes of cells invasion and migration.Results LncRNA-C21orF96 showed a significant inverse relationship with miR-875-5p,(SGC-7901:21.19 ±1.09 vs.3.28 ±0.06,P<0.01;SNU-16:24.76 ±2.09 vs.8.16 ±0.07,P < 0.01).In KATO-Ⅲ over-expressing lncRNA-C21 orF96,miR-875-5p expression decreased significantly while USF2 expression increased (P <0.01);In SGC-7901 with lncRNA-C21orF96 knockdown,miR-875-5p expression increased significantly while USF2 expression decreased (P < 0.05).The number of cells passing through the artificial basement membrane in the experimental group was significantly different from that in the control group (migration:216.19 ± 2.30 vs.89.19 ± 4.60,P<0.001;invasion:146.18 ±5.3 vs.59.18 ± 2.60,P < 0.001).Conclusions The overexpression of lncRNA-C21orF96 significantly reduces the expression of miR-875-5p and promotes the expression of USF2,hence promoting the invasion and metastasis of gastric cancer.
7.Case series study on efficacy and safety of Omalizumab in the treatment of moderate-to-severe allergic asthma in children
Lin YU ; Huishan ZHANG ; Xin ZHAO ; Wei DING ; Yanxia ZHOU ; Mei BAI ; Hongju ZHANG ; Leping YE
Chinese Journal of Applied Clinical Pediatrics 2020;35(8):617-621
Objective:To explore the clinical efficacy and safety of the new targeted anti-immunoglobulin E (IgE) drug Omalizumab in the treatment of children with moderate and severe allergic bronchial asthma in China.Methods:The clinical data of children with moderate and severe allergic asthma who were treated in the Department of Pediatrics of Peking University First Hospital from July 2018 to January 2020 and treated with Omalizumab were retrospectively analyzed.A comparison was performed on the changes of questionnaires, including childhood asthma control test (C-ACT), pediatric asthma quality of life questionnaire (PAQLQ), mini-asthma quality of life questionnaire (Mini-AQLQ) and global evaluation of asthma treatment effectiveness (GETE), pulmonary function test, including forced expiratory volume in the first second (FEV 1), percentage to predicted value (FEV 1% pred) and small airway function, fractional concentration of exhaled nitric oxide (FeNO) and so on, before and after treating with Omalizumab. Results:A total of 15 pediatric patients completed 16 weeks of treatment follow-up.After 16 weeks of Omazumab treatment, the score of C-ACT increased from (16.001.66) scores to (25.38±0.64) scores ( F=11.969, P<0.001), PAQLQ increased from (118.08 ± 23.78) scores to (141.00 ± 11.91) scores ( F=9.289, P=0.001), Mini-AQLQ increased from (78.93±7.43) scores to (97.92±3.12) scores ( F=4.145, P=0.042), and GETE decreased from (2.47±0.27) scores to (1.60±0.19) scores ( t=2.982, P=0.010). The actual value of FEV 1, FEV 1% pred, the maximum expiratory flow percentage of the predicted value (PEF% pred), forced expiratory flow at 25% (MEF 75), forced expiratory flow at 50% (MEF 50) and maximum midexpiratory flow (MMEF 75/25), increased from (1.96±0.12) L to (2.17±0.21) L ( F=0.425, P=0.789), (81.46±2.85)% to (82.64±1.55)% ( F=0.926, P=0.465), (82.05±3.58)% to (91.10±4.67)% ( F=1.909, P=0.128), (60.36±7.43)% to (76.94±4.65)% ( F=2.120, P=0.096), (52.72±3.75)% to (73.80±8.34)% ( F=3.140, P=0.047) and (60.05±8.47)% to (74.86±10.85)% ( F=7.860, P=0.010), respectively.FeNO decreased from 25.0 (14.5, 35.5) μg/L to 20.0 (18.5, 30.0) μg/L ( Z=-0.206, P=0.840). Transient headache was observed in 1 case and evanescent eruption in 2 cases during the treatment, respectively. Conclusions:Omalizumab can significantly improve the clinical manifestations, lung function indicators and quality of life of children with moderate and severe allergic asthma, and has good safety.Thus, it is expected to play an important role in the treatment of children with moderate-to-severe allergic asthma.
8. Thrombosis after establishing internal jugular vein channel in one burn patient
Yunle MENG ; Leping SUN ; Yihong ZHOU ; Chang JING ; Qi WANG ; Dongri LI
Chinese Journal of Burns 2019;35(5):395-397
On September 7th, 2017, one female patient, aged 48 years with deep partial-thickness flame burn on face, upper limbs, trunk, and lower limbs of 40% total body surface area was admitted to the First People′s Hospital of Foshan City. After admission, active fluid replacement, anti-infection, nutritional support, and other treatments were performed. After debridement and skin grafting for 3 times and blood transfusion for 2 times, the patient recovered well. On the 20th day post admission, sudden heartbeat and respiratory arrest happened, and the patient died after ineffective rescue. Autopsy showed that thrombus formed in right internal jugular vein and deep veins of lower extremities, and vascular lumina of the bilateral pulmonary artery. The direct cause of death was acute pulmonary thromboembolism, but whether the embolus originated from deep vein of lower extremity or right internal jugular vein was not clear. This case suggests that clinician should not only pay attention to the prevention of deep venous thrombosis of lower extremities of burn patients, but also the possibility of internal jugular vein thrombosis, especially for patients with internal jugular vein access.
9.Morphological analysis of cardiac rupture due to blunt injury, cardiopulmonary resuscitation and myocardial infarction in forensic pathology.
Dianshen WANG ; Fu ZHANG ; Yunle MENG ; Yangeng YU ; Kai ZHOU ; Leping SUN ; Qi MIAO ; Dongri LI
Journal of Southern Medical University 2018;38(12):1514-1520
OBJECTIVE:
To analyze the morphological features and forensic pathological characteristics of cardiac ruptures of different causes for their differential diagnosis.
METHODS:
We analyzed the data of 44 autopsy cases of cardiac rupture from 2014 to 2017 in our institute, including 11 cases caused by blunt violence with intact pericardium, 4 caused by cardiopulmonary resuscitation (CPR), 9 by myocardial infarction, and 20 by aorta dissection rupture.The gross features and histopathological characteristics of cardiac rupture and pericardial effusion were analyzed and compared.
RESULTS:
Cardiac ruptures caused by blunt violence varied in both morphology and locations, and multiple ruptures could be found, often accompanied with rib or sternum fractures; the volume of pericardial effusion was variable in a wide range; microscopically, hemorrhage and contraction band necrosis could be observed in the cardiac tissue surrounding the rupture.Cardiac ruptures caused by CPR occurred typically near the apex of the right ventricular anterior wall, and the laceration was often parallel to the interventricular septum with frequent rib and sternum fractures; the volume of pericardial blood was small without blood clots; microscopic examination only revealed a few hemorrhages around the ruptured cardiac muscular fibers.Cardiac ruptures due to myocardial infarction caused massive pericardial blood with blood clots, and the blood volume was significantly greater than that found in cases of CPR-induced cardiac rupture ( < 0.05);lacerations were confined in the left ventricular anterior wall, and the microscopic findings included myocardial necrosis, inflammatory cell infiltration, and mural thrombus.Cardiac tamponade resulting from aorta dissection rupture was featured by massive pericardial blood with blood clots, and the blood volume was much greater than that in cases of cardiac ruptures caused by blunt violence, myocardial infarction and CPR ( < 0.05).
CONCLUSIONS
Hemorrhage, inflammatory cell infiltration, and lateral thrombi around the cardiac rupture, along with pericardial blood clots, are all evidences of antemortem injuries.
Aneurysm, Dissecting
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complications
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Aortic Aneurysm
;
complications
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Cardiopulmonary Resuscitation
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adverse effects
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Forensic Pathology
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Heart Rupture
;
etiology
;
pathology
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Heart Rupture, Post-Infarction
;
pathology
;
Humans
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Myocardial Contusions
;
complications
10.Genotype, phenotype, and follow-up of Chinese patients with Gitelman's syndrome
Leping SHAO ; Jingru LU ; Yanhua LANG ; Limin ZHOU ; Cui WANG ; Ting LIU
Chinese Journal of Endocrinology and Metabolism 2017;33(1):40-46
Objective To analyze the characteristics of the genotype, phenotype, and follow-up of Gitelman's syndrome (GS) in the largest group of Chinese patients. Methods Sixty seven patients with GS underwent SLC12A3 gene analysis. Clinical characteristics and biochemical findings at the first presentation as well as follow-up were reviewed. Additionally, the associations of genotypes and phenotypes were explored. Results Forty-one different SLC12A3 mutations were identified in 67 patients with GS, including 11 novel ones, and 5 recurrent ones. 3 families (5. 7% ) had triple SLC12A3 mutations. Typical hypocalciuria and hypomagnesemia were not found in 6(9% ) and 8 (11. 9% )patients, respectively. In addition, male patients had an earlier age of onset and a higher urinary fraction excretion of electrolytes. 2 patients presented with chronic kidney disease, 13 (19. 4% ) with type 2 diabetes, 14 (20. 9% )with impaired glucose tolerance, and 5(7. 5% ) with impaired fasting glucose. Conclusion This study revealed 41 mutations in 67 Chinese patients with GS, including 11 novel variants and 5 high-frequency ones. Fraction excretion of electrolyte in urine may be more sensitive in the evaluation of phenotype compared with those of blood. It is difficult to correct hypokalemia and hypomagnesemia in GS. Patients with GS are at higher risk of the development of diabetes than ordinary people.

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