Tag: pubmed

Lakartidningen. 2021 Jul 23;118:21120.

ABSTRACT

Infection fatality ratio (IFR) in covid-19 is highly debated in international and Swedish press. In Sweden, three different estimates have been used to estimate mortality, based on statistics either from the Swedish National Board of Health and Welfare, and the Public Health Agency of Sweden, whereas excess mortality calculated by EuroMOMO. Mortality is based on death certificates, which can be accurate or erroneous, but previous analyses have suggested that over- and underdiagnosis usually even out. EuroMOMO on the other hand reports all-cause mortality compared to an estimated baseline. In view of high correlation between the different measures, we suggest that mortality is relatively correctly reported in Sweden. We discuss IFR internationally and in Sweden, and suggest that IFR in the Western world is approximately 0.5-1%. However, these numbers will change over time depending on immunity induced by vaccination efforts, but also the potential spread of new virus variants.

PMID:34296754

Dev Med Child Neurol. 2021 Jul 23. doi: 10.1111/dmcn.14993. Online ahead of print.

ABSTRACT

AIM: To investigate neurodevelopmental outcome of children with open prenatal spina bifida aperta (SBA) repair.

METHOD: Prenatal SBA repair was performed in 130 fetuses at the Zurich Center between 2010 and 2019. Seventy-seven children underwent 1 year assessment with the Griffiths Mental Developmental Scales (Griffiths) and 65 with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years. Anatomical and functional level and ambulation status were assessed. Descriptive statistics and multiple linear regression analyses for risk factors were performed.

RESULTS: The Bayley-III cognition composite score in children with prenatal SBA repair was within normal limits but lower compared to population norms (mean=95.15, SD=14.683 vs norm=100, SD=15, p=0.01). Fine motor development (mean=9.58, SD=2.744, p=0.227) was typical while gross motor development was lower than the norm (mean=3.02, SD=2.758 vs norm=10, SD=3, p<0.001). Griffiths developmental quotient subscales correlated significantly with corresponding Bayley-III scores (all p<0.001, r=0.519-0.594). At 2 years, 50.8% could walk.

INTERPRETATION: Children with non-trial open prenatal SBA repair show favourable cognitive outcome in the low-average range at 1 and 2 years of age. While gross motor function remained delayed, fine motor function was age appropriate. The correlation between Griffiths and Bayley-III allows a prediction about neurodevelopmental outcome at the age of 1 year.

PMID:34296763 | DOI:10.1111/dmcn.14993

Can J Surg. 2021 Jul 23;64(4):E403-E406. doi: 10.1503/cjs.000620.

ABSTRACT

BACKGROUND: The federal Cannabis Act came into force on Oct. 17, 2018, in Canada, making Canada only the second country in the world to legalize the cultivation, acquisition, possession and consumption of cannabis and its by-products. This provided a unique opportunity to evaluate the impact of this legislation on drug-related trauma.

METHODS: We performed a prospective observational study on the use of cannabis and other illicit drugs in the trauma population at a lead Canadian trauma centre in London, Ontario, in the 3 months before (July 1 to Sept. 30, 2018) and 3 months after (Nov. 1, 2018, to Jan. 31, 2019) the legalization of cannabis in Canada. We defined cannabis use as a positive cannabinoid screen result at the time of assessment by the trauma team. We also screened for opioids, amphetamines and cocaine.

RESULTS: A total of 210 patients were assessed by our trauma service between July 1 and Sept. 30, 2018, and 141 patients were assessed between Nov. 1, 2018, and Jan. 31, 2019. Motor vehicle collisions were the most common cause of trauma both before (101 [48.1%]) and after (67 [47.5%]) legalization. The mean Injury Severity Score was 17.6 (standard deviation [SD] 13.0) and 19.7 (SD 14.8), respectively. Drug screens were done in 88 patients (41.9%) assessed before legalization and 99 patients (70.2%) assessed after legalization. There was no difference in the rate of positive cannabinoid screen results before and after legalization (22 [25%] v. 22 [22%]). There was a trend toward higher rates of positive cannabinoid screen results (2/10 [20%] v. 5/8 [62%]) and positive toxicology screen results (5/10 [50%] v. 6/8 [75%]) after legalization among patients with penetrating trauma, but our sample was too small to achieve statistical significance.

CONCLUSION: We found no difference in the rates of positive cannabinoid screen results among patients assessed at our trauma centre in the 3 months before and the 3 months after legalization of cannabis; however, there was a trend toward an increase in the rates of positive results of toxicology screens and cannabinoid screens among those with penetrating trauma. These preliminary single-centre data showing no increased rates of cannabis use in patients with trauma after legalization are reassuring.

PMID:34296708 | DOI:10.1503/cjs.000620

Cereb Cortex. 2021 Jul 23:bhab270. doi: 10.1093/cercor/bhab270. Online ahead of print.

NO ABSTRACT

PMID:34296751 | DOI:10.1093/cercor/bhab270

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Jun;33(6):748-751. doi: 10.3760/cma.j.cn121430-20210203-00197.

ABSTRACT

OBJECTIVE: To analyze the possible causes of arrhythmia in patients receiving continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA).

METHODS: A retrospective cohort study was conducted. All patients underwent RCA-CRRT treatment from January 1, 2020 to October 31, 2020 in the intensive care unit (ICU) of Tianjin Third Central Hospital were enrolled. The patients were divided into arrhythmia group and non-arrhythmia group according to whether arrhythmia occurred. The gender, age, acute physiology and chronic health evaluation II (APACHE II) score, catheterization site, underlying diseases, electrocardiogram (ECG), electrolytes [total calcium, serum free calcium (iCa²⁺), phosphorus, magnesium, potassium] and blood gas analysis (pH value, HCO₃^–) of patients in the two groups were recorded. The changes of ECG were observed, the differences in electrolyte and blood gas analysis indexes between the two groups of patients at different time points (before CRRT, 24, 48, 72 hours after CRRT, and when arrhythmia occurred) were compared.

RESULTS: A total of 86 RCA-CRRT patients were enrolled, of which 12 cases (13.95%) had arrhythmia, and the remaining 74 cases (86.05%) had no arrhythmia. The average time for the occurrence of arrhythmia in the 12 patients was (44.00±16.82) hours. There was no significant ST-segment change in the ECG when the arrhythmia occurred compared with that before CRRT, the total calcium level was significantly higher than that before CRRT (mmol/L: 2.48±0.40 vs. 2.13±0.35, P < 0.05), the blood magnesium level was significantly lower than that before CRRT (mmol/L: 0.73±0.20 vs. 0.95±0.25, P < 0.05). There was no significant difference in iCa²⁺, blood phosphorus, blood potassium, pH value and HCO₃^– between before CRRT and when arrhythmia occurred. Over time, the total calcium levels in the two groups increased, and there was a statistical difference between the 48 hours after CRRT and before CRRT (mmol/L: 2.48±0.33 vs. 2.13±0.35 in the arrhythmia group, and 2.30±0.22 vs. 2.15±0.48 in non-arrhythmia group, both P < 0.05). The linear change trend of iCa²⁺, pH value and HCO₃^– was not obvious in the two groups. The blood phosphorus and blood magnesium levels in the two groups decreased. The blood potassium in the arrhythmia group decreased, however, the blood potassium level in non-arrhythmia group did not change significantly. The total calcium level in the arrhythmia group was significantly higher than that in the non-arrhythmia group at 72 hours after CRRT (mmol/L: 2.69±0.35 vs. 2.45±0.23, P < 0.05); however, there was no significant difference in serum iCa²⁺, phosphorus, magnesium, potassium, pH value and HCO₃^– between the two groups.

CONCLUSIONS: Patients receiving RCA-CRRT were less likely to develop arrhythmia, the causes may be related to the accumulation of citric acid and electrolyte disturbances such as calcium, phosphorus, and magnesium.

PMID:34296699 | DOI:10.3760/cma.j.cn121430-20210203-00197

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Jun;33(6):752-754. doi: 10.3760/cma.j.cn121430-20201231-00787.

ABSTRACT

OBJECTIVE: To observe the effect of two different screening scales used by 120 dispatchers to early identify stroke patients and give telephone guidance for treatment.

METHODS: From October 2018 to August 2019, 2 027 stroke and suspect stroke patients who called the Kaifeng 120 Emergency Center were enrolled. The differences in the final positive rate of stroke diagnosis and the incidence of adverse events were compared and analyzed in 1 020 cases using recognition of stroke in the emergency room (ROSIER) and 1 007 cases using facial drooping, arm weakness, speech difficulties and time (FAST) scale scores for telephone guidance.

RESULTS: The positive rate of stroke identification in ROSIER score group was higher than that in FAST score group [31.4% (320/1 020) vs. 29.3% (295/1 007)], the false report rate was significantly lower than that in FAST score group [14.9% (152/1 020) vs. 18.8% (189/1 007), P < 0.05], the incidence of adverse events caused by vomiting, falling from bed and convulsions in ROSIER score group were lower than those in FAST score group [0.5% (1/208) vs. 2.2% (4/185), 0% (0/26) vs. 20.0% (2/10), 2.1% (1/48) vs. 10.3% (3/29)], however, the incidence of adverse events caused by falling out of bed was significantly lower (P < 0.05). The incidence of total adverse events in ROSIER score group was significantly lower than that in FAST score group [0.7% (2/305) vs. 3.8% (9/235), P < 0.05]. The time of FAST score group was shorter than that of ROSIER score group (minutes: 1.2±0.2 vs. 2.5±0.3), but the difference was not statistically significant (P > 0.05).

CONCLUSIONS: Two different scales can be used to early identify stroke patients and provide timely pre-hospital guidance, thus reduce the incidence of adverse events. Although the ROSIER score takes longer time, the dispatchers guide the patients by phone which does not affect the dispatch time.

PMID:34296700 | DOI:10.3760/cma.j.cn121430-20201231-00787

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Jun;33(6):692-696. doi: 10.3760/cma.j.cn121430-20210116-00074.

ABSTRACT

OBJECTIVE: To observe the application effect of high-flow nasal canula oxygen therapy (HFNC) after extubation in patients with mechanical ventilation (MV) in the intensive care unit (ICU).

METHODS: A prospective study was conducted. From January 2018 to June 2020, 163 MV patients admitted to Yijishan Hospital of Wannan Medical College were enrolled, and they were divided into HFNC group (82 cases) and traditional oxygen therapy group (81 cases) according to the oxygen therapy model. The patients included in the study were given conventional treatment according to their condition. In the HFNC group, oxygen was inhaled by a nasal high-flow humidification therapy instrument. The gas flow was gradually increased from 35 L/min to 60 L/min according to the patient’s tolerance, and the temperature was set at 34-37 centigrade. The fraction of inspiration oxygen (FiO₂) was set according to the patient’s pulse oxygen saturation (SpO₂) and SpO₂ was maintained at 0.95-0.98. A disposable oxygen mask or nasal cannula was used to inhale oxygen in the traditional oxygen therapy group, and the oxygen flow was 5-8 L/min, maintaining the patient’s SpO₂ at 0.95-0.98. The differences in MV duration before extubation, total MV duration, intubation time, reintubation time, extubation failure rate, ICU mortality, ICU stay, and in-hospital stay were compared between the two groups, and weaning failure were analyzed.

RESULTS: There was no significant differences in MV duration before extubation (days: 4.33±3.83 vs. 4.15±3.03), tracheal intubation duration (days: 4.34±1.87 vs. 4.20±3.35), ICU mortality [4.9% (4/82) vs. 3.7% (3/81)] and in-hospital stay [days: 28.93 (15.00, 32.00) vs. 27.69 (15.00, 38.00)] between HFNC group and traditional oxygen therapy group (all P > 0.05). The total MV duration in the HFNC group (days: 4.48±2.43 vs. 5.67±3.84) and ICU stay [days: 6.57 (4.00, 7.00) vs. 7.74 (5.00, 9.00)] were significantly shorter than those in the traditional oxygen therapy group, the reintubation duration of the HFNC group was significantly longer than that of the traditional oxygen therapy group (hours: 35.75±10.15 vs. 19.92±13.12), and the weaning failure rate was significantly lower than that of the traditional oxygen therapy group [4.9% (4/82) vs. 16.0% (13/81), all P < 0.05]. Among the reasons for weaning failure traditional oxygen therapy group had lower ability of airway secretion clearance than that of the HFNC group [8.64% (7/81) vs. 0% (0/82), P < 0.05], there was no statistically differences in the morbidity of heart failure, respiratory muscle weakness, hypoxemia, and change of consciousness between the two groups.

CONCLUSIONS: For MV patients in the ICU, the sequential application of HFNC after extubation can reduce the rate of weaning failure and the incidence of adverse events, shorten the length of ICU stay.

PMID:34296688 | DOI:10.3760/cma.j.cn121430-20210116-00074

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Jun;33(6):721-726. doi: 10.3760/cma.j.cn121430-20210323-00427.

ABSTRACT

OBJECTIVE: To analyze risk factors for the occurrence and progression of isolated distal deep vein thrombosis (IDDVT) of lower limbs, and to explore the predictive value of dynamic changes of coagulation index D-dimer on the occurrence and progression of IDDVT in acute brain injury (ABI) patients during perioperative period.

METHODS: A retrospective case-control study was conducted. Perioperative ABI patients admitted to department of neurocritical care unit (NCCU) of the First Affiliated Hospital of University of Science and Technology of China from September 2019 to May 2020 were enrolled. Patients’ baseline characteristics, disease characteristics, treatment approaches, outcomes and coagulation function index at 1, 2-4, 5-7 and > 7 days post operation were analyzed between patients with IDDVT and patients with progressive IDDVT. Risk factors for IDDVT occurrence and progression were identified by multivariate Logistic regression. Receiver operating characteristic curve (ROC curve) were drawn to assess the predictive value of coagulation indexes for IDDVT occurrence and progression.

RESULTS: A total of 164 ABI patients were enrolled. Most of the patients were elderly [age was 60 (51, 69) years], male [99 cases (60.4%)], and severe cases [Glasgow coma score (GCS) at admission was 6 (5, 8)]. The rates of IDDVT occurrence and progression were 61.6% (101 cases) and 16.8% (17 cases), respectively, the rate of proximal deep venous thrombosis (DVT) was 12.8% (21 cases). Compared with the IDDVT group (101 patients), patients without IDDVT group were younger (years: 55±13 vs. 62±13), length of intensive care unit (ICU) stay were shorter (days: 12±6 vs. 15±7), body mass index (BMI) and GCS at admission were higher [59 patients, BMI (kg/m²): 23±5 vs. 19±8, GCS scores: 7±2 vs. 6±2], the differences were statistically significant (all P < 0.05). Compared with patients with IDDVT progression group, male patients were fewer [61.9% (52/84) vs. 88.2% (15/17)], the proportion of transfusion of red blood cell and anticoagulant therapy were lower [8.3% (7/84) vs. 29.4% (5/17) and 47.6% (40/84) vs. 94.1% (16/17)], the proportion of cerebral herniation was higher [42.9% (38/84) vs. 11.8% (2/17)] in patients without IDDVT progressive group. All of the differences were statistically significant (all P < 0.05). D-dimer were increased in two groups of whether IDDVT occurrence or not over time. D-dimer peaked on 5-7 days after surgery in IDDVT occurrence group, and then decreased. D-dimer peaked at > 7 days after surgery in patients without IDDVT. With time, D-dimer were increased in groups of whether IDDVT progression or not, both peaked at 5-7 days postoperation, and then decreased. Compared with non-IDDVTgroup, D-dimer was significantly increased in IDDVT group from 2-4 days after surgery [mg/L: 4.1 (2.3, 8.0) vs. 2.4 (1.7, 3.4), P < 0.05], and lasted until 5-7 days [mg/L: 5.5 (3.3, 11.4) vs. 3.9 (2.6, 5.8), P < 0.05]. Compared with IDDVT group, D-dimer was significantly increased in IDDVT progressive group from 2-4 days [mg/L: 11.2 (4.7, 20.0) vs. 3.7 (2.1, 6.8), P < 0.05], and lasted until 7 days [mg/L: 11.0 (3.0, 18.9) vs. 4.1 (2.6, 6.5), P < 0.05]. Multivariate Logistic regression analysis showed that age > 60 years [odds ratio (OR) = 3.43, 95% confidence interval (95%CI) was 1.69-6.96, P = 0.001], GCS score at admission > 8 (OR = 0.35, 95%CI was 0.17-0.76, P = 0.008), length of ICU stay > 13 days (OR = 2.25, 95%CI was 1.08-4.70, P = 0.031) were risk factors for IDDVT. Gender (OR = 0.19, 95%CI was 0.02-0.71, P = 0.019), transfusion of red blood cell (OR = 6.50, 95%CI was 1.33-31.94, P = 0.021), cerebral herniation (OR = 0.18, 95%CI was 0.37-0.90, P = 0.036) were risk factors for IDDVT profression. ROC curve analysis showed that age and D-dimer at 5-7 days were predicators of IDDVT [the area under curve ROC (AUC) were 0.68 and 0.72, 95%CI were 0.60-0.75 and 0.64-0.80, both P value were 0.000 1]. When the cut-off value of age was 60 years old and the D-dimer was 5.4 mg/L, the sensitivity were 60.6% and 54.4%, specificity were 71.2% and 80.9%, respectively, positive predictive value were 78.7%, 84.5%, negative predictive value were 51.2%, 48.1%, respectively. The elevation of D-dimer to 3.9 times at days 5-7 compared with day 1 of NCCU stay was a predicator of IDDVT progression (AUC = 0.81, 95%CI was 0.71-0.88, P = 0.000 1). The sensitivity, specificity, positive predictive value and negative predictive value were 76.5%, 74.6%, 41.9% and 93.0%, respectively.

CONCLUSIONS: IDDVT occurrence and progressiveare common in severe ABI patients during perioperative period. The dynamic change of D-dimer, especially at days 5-7, is a valuable predictor of IDDVT progressionin ABI patients, which is helpful for guiding implementation of deep vein ultrasound of lower limb.

PMID:34296693 | DOI:10.3760/cma.j.cn121430-20210323-00427

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Jun;33(6):654-658. doi: 10.3760/cma.j.cn121430-20210424-00605.

ABSTRACT

OBJECTIVE: To investigate the predictive value of heparin binding protein (HBP) for sepsis.

METHODS: From June 2019 to December 2020, 188 patients admitted to the department of emergency of Hunan Provincial People’s Hospital were enrolled. The patients were divided into non-sepsis group (87 patients) and sepsis group (101 patients) according to Sepsis-3 criteria. Gender, age, white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), HBP, sequential organ failure assessment (SOFA) score, quick SOFA (qSOFA) score, modified early warning score (MEWS) and patients’ recent medication history were recorded, the differences in the above indicators between the two groups were compared. The risk factors of sepsis were analyzed by Logistic regression. Spearman correlation analysis was used to analyze the correlation between HBP, PCT, CRP and SOFA score to evaluate the predictive value of HBP, PCT and CRP for the severity of septic organ failure. Receiver operating characteristic curve (ROC curve) were drawn to evaluate the diagnostic value of HBP, PCT and CRP for sepsis.

RESULTS: Compared with the non-sepsis group, the sepsis group had significantly higher levels of HBP, PCT, CRP, WBC, SOFA score, qSOFA score, and MEWS [HBP (μg/L): 55.46 (24.57, 78.49) vs. 5.90 (5.90, 9.01), PCT (μg/L): 6.83 (1.75, 30.64) vs. 0.23 (0.12, 0.75), CRP (mg/L): 67.35 (26.23, 123.23) vs. 4.45 (2.62, 47.22), WBC (×10⁹/L): 11.84 (7.18, 16.06) vs. 6.58 (5.47, 8.99), SOFA score: 6 (4, 8) vs. 0 (0, 0), qSOFA score: 2 (1, 3) vs. 0 (0, 1), MEWS: 4 (3, 6) vs. 1 (0, 2)], the length of hospital stay was significantly prolonged [days: 10 (4, 17) vs. 0 (0, 7)], and the mortality was significantly increased [29.7% (30/101) vs. 4.6% (4/87)], with statistical significance (all P < 0.05). Correlation analysis showed that HBP, PCT and CRP were significantly positively correlated with SOFA score (r values were 0.60, 0.33, and 0.38, respectively, all P < 0.01), among which HBP had the strongest correlation, CRP was the second, and PCT was the weakest. Logistic regression analysis showed that HBP, PCT and CRP levels were independent risk factors for sepsis [odds ratio (OR) were 1.015, 1.094, 1.067, 95% confidence intervals (95%CI) were 1.007-1.022, 1.041-1.150, 1.043-1.093, all P < 0.01]. ROC curve analysis showed that HBP, PCT and CRP all had some diagnostic value for sepsis [the area under ROC curve (AUC) were 0.92, 0.87, 0.80, 95%CI were 0.88-0.97, 0.82-0.92, 0.74-0.87, respectively, all P < 0.01]. Among them, the diagnostic efficacy of HBP was higher when the cut-off value was ≥ 15.11 μg/L, its sensitivity and specificity were 86.14% and 89.66%, respectively, which were higher than the sensitivity (81.19%) and specificity (80.46%) when the PCT cut-off value was ≥ 1.17 μg/L. However, CRP had the best sensitivity of 94.06% for the diagnosis of sepsis but lacked of specificity (63.22%).

CONCLUSIONS: HBP can be used as a biological indicator for predicting sepsis and can assess the severity of organ failure in septic patients.

PMID:34296681 | DOI:10.3760/cma.j.cn121430-20210424-00605

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Jun;33(6):665-670. doi: 10.3760/cma.j.cn121430-20210325-00437.

ABSTRACT

OBJECTIVE: To evaluate the clinical value of neutrophil/lymphocyte ratio (NLR) in early prediction of the incidence of sepsis-induced organ dysfunction and 28-day mortality.

METHODS: A retrospective study was conducted in 815 adult patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of China Medical University from January 2017 to December 2019. The clinical data including age, gender and complication were collected, and the peripheral blood routine indexes at 24, 48 and 72 hours after the diagnosis of sepsis were collected, and the NLR was calculated. The primary endpoint of the study was the incidences of sepsis related acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and acute liver failure (ALF); the secondary endpoint was the 28-day in-hospital mortality in septic patients with organ dysfunction. Univariate and multivariate Logistic regression were used to analyze the risk factors of organ dysfunction and 28-day mortality in patients with sepsis, the receiver operating characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of NLR for organ dysfunction and 28-day mortality in patients with sepsis.

RESULTS: A total of 714 patients with sepsis were enrolled for final statistical analysis. There was no significant difference in NLR at 24, 48 and 72 hours in patients with or without organ dysfunction (such as AKI, ARDS, DIC and ALF). Logistic regression analysis showed that there was no significant difference in NLR at 24 hours with 28-day in-hospital mortality [odds ratio (OR) = 1.006, 95% confidence interval (95%CI) was 0.994-1.019, P = 0.323]. However, NLR at 48 hours and 72 hours had a significant difference with 28-day mortality (48 hours: OR = 1.026, 95%CI was 1.013-1.040, P = 0.000; 72 hours: OR = 1.021, 95%CI was 1.005-1.037, P = 0.010), which suggested that NLR at 48 hours and 72 hours after diagnosis were independent risks factor for 28-day mortality in patients with sepsis. ROC curve showed that the AUC of NLR at 48 hours was 0.598, 95%CI was 0.540-0.658, P = 0.02; when the cut-off value was 10.1, the sensitivity and specificity for predicting 28-day mortality was 75.2% and 58.0%, respectively; the AUC of NLR at 72 hours was 0.595, 95%CI was 0.536-0.655, P = 0.03; when the cut-off value was 9.24, the sensitivity and specificity for predicting 28-day mortality was 75.3% and 59.9%, respectively.

CONCLUSIONS: NLR cannot predict the occurrence of AKI, ARDS, DIC and ALF in sepsis in early stage. NLR has a certain clinical value in predicting 28-day mortality in patients with sepsis, but its predictive efficiency is low.

PMID:34296683 | DOI:10.3760/cma.j.cn121430-20210325-00437