Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt / 中华肝脏病杂志

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia / 中华内科杂志

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.

Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population / 中国医学科学院学报

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

Effects of Li-Dan-He-Ji on regulating oxidative stress and antagonising infantile cholestatic hepatic fibrosis / 中华危重病急救医学

OBJECTIVE@#To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis.@*METHODS@#Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups.@*RESULTS@#During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05).@*CONCLUSIONS@#The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.

Clinical and genetic diagnosis for 26 paitents with hereditary spherocytosis / 中南大学学报(医学版)

OBJECTIVES@#Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of ANK1, SPTB, SPTA1, SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis.@*METHODS@#Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (UGT1A1), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared.@*RESULTS@#Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. SPTB mutations (12) and ANK1 mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the SPTB mutant group and the ANK1 mutant group (all P>0.05). The rate of splenectomy in ANK1 mutation group was higher than that in SPTB mutation group, and the difference was statistically significant (χ2=6.970, P=0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all P>0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent UGT1A1 mutation detection, among which 5 patients carried UGT1A1 mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, P=0.038).@*CONCLUSIONS@#Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.

Interpretation of the 2022 American Academy of Pediatrics guidelines for the management of hyperbilirubinemia in newborn infants / 中国当代儿科杂志

The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.

Nonalcoholic fatty liver disease and bilirubin: correlation, mechanism, and therapeutic perspectives / 中华肝脏病杂志

Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.

A real-world study of the effects of endocrine therapy on liver function in breast cancer / 中华外科杂志

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

Análise macroscópica e radiográfica de dentes decíduos com hiperbilirrubinemia de crianças com doenças hepáticas crônicas e transplante hepático / Macroscopic and radiographic analysis of primary teeth with hyperbilirubinemiain children with chronic liver disease and liver transplantation

Objetivo: identificar mediante análise macroscópica e ra-diográfica as alterações estruturais em tecidos dentários afetados pela hiperbilirrubinemia, normalmente constatada a partir do sinal clínico de icterícia e provoca o desenvolvi-mento de pigmentos intrínsecos esverdeados nas estruturas dentárias. Materiais e Métodos: a amostra foi composta por 31 dentes decíduos dividida em grupo controle (n= 7) e grupo experimental (n= 24). As análises macroscópicas foram efetuadas por meio de fotografias individuais padroniza-das e as radiográficas obtidas com aquisições de imagem a 9 mA, 70 kVp, distância de 8cm, exposição 0,4 segundos e com XDR Sensor®. As imagens foram convertidas pelo software XDR Brasil 3.1.6 e padronizadas pelo programa GIMP 2.10.22. Os dados da média simples do histograma foram analisados pelo teste T-Student e Mann-Whitney (p<0,05). Resultados: demonstraram a maior intensidade de pigmentação em região cervical da raiz, com diferença de densidade radiográfica estaticamente significante na porção radicular entre os grupos experimental e controle (p=0,043). Na análise da densidade radiográfica da estrutura radicular do grupo experimental houve diferença estatica-mente significante (p=0,016) entre os terços cervical e apical. Discussão: Os dados evidenciaram que dentes pigmentados pela hiperbilirrubinemia não possuem alterações na densidade mineral nos terços coronários. Conclusão: Dentes com pigmentação esverdeada bilirrubina possuem diferenças na densidade radiográfica so-mente na região radicular.

Aim: is to identify, through macroscopic and radio-graphic analysis, structural changes in dental tissues affected by hyperbilirubinemia, usually seen from the clinical sign of icterus and causes the development of intrinsic greenish pigments in dental structure. Materials and Methods: The sample consisted of 31 primary teeth divided into a control group (n=7) and an experimental group (n=24). Macroscopic analyzes were performed using standardized individual photographs and radiographic ones obtained by image acquisition at 9 mA, 70 kVp, 8cm distance, 0.4 seconds exposure and with XDR Sensor®. The images were converted by XDR Brasil 3.1.6 software and standardized by GIMP 2.10.22 software. The Histogram's simple mean data were analyzed by T-Student and Mann-Whitney tests (p<0.05). Results: showed intensity of pigmentation in the cervical region of the root, with a statistically significant difference in the root portion between the experimental and control groups (p=0.043. In the analysis of radiographic density of the root structure of the experimental group, there was a statistically significant difference (p= 0.016) between the cervical and apical thirds. Discussion: The data showed that teeth pigmented by hyperbilirubinemia do not have changes in mineral density in the coronary thirds. Conclusion: Greenish pigments teeth have differences in radiographic density only in the root structure.

Validación de un método analítico para cuantificación de ferritina en líquido cefalorraquídeo / Validation of an analytical method for the quantification of ferritin in cerebrospinal fluid

Resumen La ferritina es una proteína de gran tamaño que se encuentra fisiológicamente en el líquido cefalorraquídeo (LCR) en concentraciones de 2-10 ng/mL. Su elevación puede utilizarse como biomarcador en distintas condiciones patológicas. El procedimiento de validación tradicional para la medición en LCR no puede ser utilizado debido a la ausencia de controles y calibradores comerciales para esta matriz. El objetivo de este trabajo fue llevar a cabo una validación analítica de ferritina en LCR. Se realizaron ensayos de estimación de precisión y veracidad mediante el protocolo EP15-A3, linealidad por el protocolo EP6-A (ambos de la guía de la CLSI), recuperación, estabilidad, contaminación por arrastre, interferencia por hemólisis y bilirrubina y límite de detección (LoD). La ferritina en LCR en el autoanalizador DxI 800 de Beckman Coulter tuvo una performance intra e interensayo <3,7%, el ensayo denota linealidad en el intervalo de 2,1-547 ng/mL; se estableció estabilidad por un período de 5 días y la recuperación resultó ser aceptable. No se evidenció efecto de contaminación por arrastre ni interferencia por hemólisis hasta un rango entre 300-500 mg/dL de hemoglobina, ni interferencia por bilirrubina hasta una concentración de 16,0 mg/dL de bilirrubina total. El LoD fue de 0,4 ng/mL. Por medio de los ensayos realizados se logró validar la ferritina en LCR a partir de la utilización de pools de muestras, lo que pudo garantizar la confiabilidad y exactitud del método analítico.

Abstract Ferritin is a large protein physiologically present in the cerebrospinal fluid (CSF) in concentrations of 2-10 ng/mL. Its elevation can be used as a biomarker in several pathological conditions. The traditional validation procedure for measurement in CSF cannot be used due to the absence of commercial controls and calibrators for this matrix. The objective of the present study was to perform CSF ferritin analytical validation. Assays such as precision and accuracy estimation through the EP15-A3 protocol, linearity according to the EP6-A protocol (both from the CLSI guidelines), recovery, stability, carry-over, hemolysis and bilirubin interference and limit of detection (LoD) were conducted. Serum samples with different concentrations of ferritin were added to aliquots of a normal CSF pool. CSF ferritin in the Beckman Coulter DxI 800 had a <3.7% intra and inter-assay performance, the assay shows linearity in the 2.1 -547 ng/mL interval, stability was established for a 5-day period and the recovery was acceptable. There was neither carry-over effect or hemolysis interference up to a range of 300-500 mg/dL of hemoglobin, nor interference by bilirubin up to 16.0 mg/dL of total bilirubin. The LoD was 0.4 ng/mL. By means of the performed assays, CSF ferritin was validated by using sample pools, thereby ensuring the reliability and accuracy of the analytical method.

Resumo A ferritina é uma grande proteína fisiologicamente encontrada no líquido cefalorraquidiano (LCR) em concentrações de 2 a 10 ng/mL. Sua elevação pode ser usada como biomarcador em diferentes condições patológicas. O procedimento de validação tradicional para medição no LCR não pode ser usado devido à ausência de controles e calibradores comerciais para esta matriz. O objetivo deste estudo foi realizar uma validação analítica da ferritina no LCR. Foram realizados estudos de precisão e veracidade utilizando o protocolo EP15-A3, linearidade pelo protocolo EP6-A (ambos das diretrizes do CLSI), recuperação, estabilidade, contaminação transportada, interferência de hemólise e bilirrubina e limite de detecção (LoD). A ferritina no LCR no DxI 800 da Beckman Coulter teve um desempenho intra e inter-ensaio <3,7%, o ensaio denota linearidade na faixa de 2,1-547 ng/mL, a estabilidade foi estabelecida em um período de 5 dias e a recuperação foi considerado aceitável. Nenhum efeito de transporte ou interferência por hemólise foi evidenciado até um intervalo entre 300-500 mg/dL de hemoglobina, nem interferência pela bilirrubina até uma concentração de 16,0 mg/dL de bilirrubina total. O LoD foi de 0,4 ng/mL. Através dos testes realizados, a ferritina no LCR foi validada, com base no uso de pool de amostras, o que poderia garantir a confiabilidade e a acurácia do método analítico.

Comparación clínica y laboratorial de la fiebre amarilla severa versus dengue grave en Perú / Clinical and laboratory differences between severe yellow fever and severe dengue in emergency patients

En los centros de Emergencia con poco apoyo de laboratorio, es difícil diferenciar a los pacientes con dengue grave y fiebre amarilla severa. El objetivo fue comparar el perfil clínico y de laboratorio de los pacientes con dengue grave y fiebre amarilla severa en Urgencias. Se realizó un estudio observacional retrospectivo de pacientes con diagnóstico confirmado de dengue y fiebre amarilla en el período 2018 a 2020 atendidos en la Unidad de Emergencia del Hospital Carrión, Huancayo-Perú. Se evaluaron un total de 35 pacientes, 11 pacientes (31,4%) fueron diagnosticados con fiebre amarilla severa y 24 pacientes (68,5%) con dengue grave. La media de los resultados de laboratorio con fiebre amarilla severa fueron bilirrubina indirecta 4,7 ml/dL, aspartato transaminasa 4463 UI/L, transaminasa aminotransferasa 4329 UI/L, creatinina 4,9 mg/dl. En pacientes con dengue grave el hematocrito promedio fue 51,8, hemoglobina 17,6 g/dl, plaquetas 24 × 103/mm. En pacientes con síndrome ictérico-febril la presencia de bradicardia, bilirrubina indirecta elevada y transaminasas muy elevadas debe hacer sospechar de fiebre amarilla; mientras que los pacientes que acuden por ascitis, derrame pleural, aumento de hematocrito y deficiencia de plaquetas, se debe tratar como dengue grave sobre todo en Unidades de Emergencia con poco apoyo de laboratorio(AU)

In Emergency centers with little laboratory support, differentiating patients with dengue and yellow fever is difficult. The Aim was to compare the clinical and laboratory profile of patients with severe dengue and severe yellow fever in the Emergency unit. We conducted a retrospective observational study of patients with a confirmed diagnosis of dengue and yellow fever in the period 2018 to 2020 treated in the Emergency Unit of the Carrión hospital, Huancayo-Peru. A total of 35 patients were evaluated, 11 patients (31.4%) were diagnosed with severe yellow fever and 24 patients (68.5%) with severe dengue. The mean laboratory results in patients with severe yellow fever were indirect bilirubin 4.7 ml/dL, aspartate transaminase 4463 IU/L, transaminase aminotransferase 4329 IU/L, creatinine 4.9 mg / dl. In patients with severe dengue were hematocrit 51.8, hemoglobin 17.6 g / dl, platelets 24 × 103 / mm. In patients with syndrome jaundice and fever the presence of bradycardia, elevated indirect bilirubin, and very elevated transaminases should be suspicious for yellow fever; while in patients who come for ascites, pleural effusion, increased hematocrit and platelet deficiency, it should be treated as severe dengue especially in Emergency Units with little laboratory support(AU)

Hiperbilirrubinemia: visión del patólogo / Hyperbilirubinemia: pathologist's view

Los niveles de bilirrubina sérica normal en el adulto varían entre 0,3 mg/dL y 1,2 mg/dL, y su valor está determinado por la tasa de captación hepática, conjugación y excreción. La ictericia se hace evidente cuando los niveles de bilirrubina sérica se elevan por encima de 2,5 mg/dL a 3 mg/dL, siendo un indicador de enfermedad subyacente. La bilis es producida por los hepatocitos y fluye desde los canalículos, canales de Hering, conductos biliares intrahepáticos, conductos hepáticos derechos e izquierdos hasta llegar al duodeno. A nivel histopatológico, cualquier entidad que lleve a la acumulación intrahepática de bilis por disfunción hepatocelular u obstrucción biliar genera colestasis, que se observa en la biopsia hepática como la acumulación de tapones de color marrón verdoso de pigmento biliar en los hepatocitos, y secundariamente se observan los canalículos dilatados. Las causas de colestasis intrahepática son diversas e incluyen enfermedades como colangitis biliar primaria, colangitis esclerosante primaria, hepatitis autoinmune, hepatitis virales y toxicidad medicamentosa. Esta revisión tiene como objetivo analizar algunos tipos de hiperbilirrubinemia, resaltando sus características histopatológicas.

Normal serum bilirubin levels in adults range from 0.3 mg/dL to 1.2 mg/dL, and its value is determined by the rate of hepatic uptake, conjugation, and excretion. Jaundice becomes apparent when serum bilirubin levels rise above 2.5 mg/dL to 3.5 mg/dL and is an indicator of underlying disease. Bile is produced by hepatocytes and flows from the canaliculi, Hering's canals, intrahepatic bile ducts, and right and left hepatic ducts to the duodenum. Pathologically, any condition that leadsto intrahepatic accumulation of bile due to hepatocellular dysfunction or biliary obstruction, generates cholestasis, which is observed in liver biopsy as the accumulation of greenish-brown deposits of bile pigment in hepatocytes, with dilated canaliculi. The causes of intrahepatic cholestasis are diverse and include diseases such as primary biliary cholangitis and primary sclerosing cholangitis, autoimmune hepatitis, viral hepatitis, and drug toxicity. This review aims to analyze some types of hyperbilirubinemia, highlighting their histopathological characteristics.

Research progress on the relationship between liver cirrhosis and thyroid hormones / 中华肝脏病杂志

There exists a complex relationship between liver and thyroid hormones. Liver plays an important role in the activation, inactivation, transportation, and metabolism of thyroid hormones. At the same time, thyroid hormones also affect hepatocytes activity and liver metabolism, such as lipid and bilirubin metabolism. Importantly, thyroid hormone levels often change abnormally in patients with liver cirrhosis. Therefore, studying the change of thyroid hormone levels in patients with liver cirrhosis has a certain clinical value for assessing the severity, prognosis, diagnosis and treatment. This paper reviews the research progress on the relationship between liver cirrhosis and thyroid hormone.

The Efficacy of Rh Phenotype Matched Blood Transfusion / 中国实验血液学杂志

OBJECTIVE@#To analyze and evaluate the efficacy of Rh phenotype matched blood transfusion.@*METHODS@#The increasing of hemoglobin (Hb) and hemolysis tests in the patients treated by Rh matched red blood cells or not, as well as the first time unmatched transfusions and the unmatched transfusions happened again after a period (≥10 d) were retrospectively analyzed.@*RESULTS@#A total of 674 times transfusions in 120 patients were evaluated. The increasing of Hb in each unit was higher in the patients treated by Rh matched blood transfusion (vs unmatched) [(33.397±1.475) g/U vs (29.951±1.304) g/U, P=0.033], while the increasing of Hb at first time unmatched transfusion and the second time unmatched transfusion was not statistically different[ (28.942±2.083) g/U vs (30.686±1.737) g/U, P=0.589]. The level of lactate dehydrogenase were related to erythrocyte washing, irradiation, period of validity and the second time unmatched transtusion (all P<0.05); the levels of total bilirubin (TBil), direct bilirubin (DBil) and indirect bilirubin (IBil) between the first time unmatched transfusion and the second time unmatched transfusion were statistically different (all P<0.05).@*CONCLUSION@#For the patients need multiple blood transfusions, Rh phenotype matched blood transfusion can reduce the exposure to Rh allogenic antigens, improve the efficacy and ensure the safety of blood transfusion.

The Correlation Analysis between the Titer of IgG Anti-A/B Erythrocyte Antibody In Vivo of the Neonate and the Severity of Hemolytic Disease of Newborn / 中国实验血液学杂志

OBJECTIVE@#To investigate the titer of IgG anti-A/B erythrocyte antibody in vivo of the neonate with hemolytic disease of newborn(HDN), and explore its clinical valua in evaluating the severity of HDN.@*METHODS@#300 neonates with HDN, 50 neonates with neonatal hyperbilirubinemiain and 50 healthy neonates were selected as research object and Microtubes Gel Test was used to detect the titer of IgG anti-A/B erythrocyte antibody in vivo. Their clinical data and their mothers' prenatal examination data were retrospectively analyzed. Three hemolysis tests (direct antiglobulin test, free antibody test and release test), irregular antibody screening, and the titer of IgG anti-A/B blood group antibody was determined by serological method. Red blood cells(RBC), hemoglobin(Hb), reticulocytes(Ret) and nucleated red cells were detected by hematology analyzer. Indirect bilirubin and albumin(Alb) were detected by biochemical analyzer. The relationship between the titer of IgG anti-A/B erythrocyte antibody in vivo and the severity of HDN was analyzed.@*RESULTS@#There were six serological diagnosis modes in the HDN group,the difference between modes was statistically significant (P<0.05). The antibody titer relationship between HDN neonates and pregnant women was positive correlation(r=0.8302). The highest antibody titer of release test and free antibody test were 1∶32 and 1∶2, and the difference was statistically significant（P<0.05）. RBC, Hb and Alb in HDN patients were lower than those in neonatal hyperbilirubinemia patients and healthy neonates (P<0.05), and were negatively relevant with antibody titer in vivo (r=-0.8016). Bilirubin content in HDN patients were higher than those in neonatal hyperbiliru binemia patients and healthy neonates group(P<0.05), and was positively relevant with antibody titer in vivo (r=0.8731). The hospital day in HDN patients was significantly relevant with the antibody titer in vivo (r=0.8547), but not with the age, sex, weight and ABO blood types (P>0.05).@*CONCLUSION@#The detection of antibody titer in HDN patients can be used to evaluate the antibody concentration in vivo, predict the ability of antibody to induce erythrocyte hemolysis, and help to judge the serenrity and prognosis of HDN.

Cord blood bilirubin and prediction of neonatal hyperbilirubinemia and perinatal infection in newborns at risk of hemolysis

Abstract Objective To assess the accuracy of umbilical cord bilirubin values to predict jaundice in the first 48 h of life and neonatal infection. Method Newborn infants treated at a regional well-baby nursery born at ≥36 weeks of gestation were included in this retrospective cohort study. All infants born in a 3-year period from mothers with O blood type and/or Rh-negative were included and had the umbilical cord bilirubin levels measured. Hyperbilirubinemia in the first 48 h was defined as bilirubin levels above the phototherapy threshold. Neonatal infection was defined as any antibiotic treatment before discharge. Results A total of 1360 newborn infants were included. Two hundred and three (14.9%) newborn infants developed hyperbilirubinemia in the first 48 h of life. Hyperbilirubinemic infants had smaller birth weight, higher levels of umbilical cord bilirubin, a higher rate of infection and were more often direct antiglobulin test positive. Umbilical cord bilirubin had a sensitivity of 76.85% and a specificity of 69.58% in detecting hyperbilirubinemia in the first 48 h, with the cut-off value at 34 µmol/L. The area under the receiver operating characteristic curve was 0.80 (95% CI: 0.78-0.82). Umbilical cord bilirubin had a sensitivity of 27.03% and specificity of 91.31% in detecting perinatal infection. The area under the receiver operating characteristic (ROC) curve was 0.59 (95% CI: 0.57-0.63). Conclusions A positive correlation was found between umbilical cord bilirubin and hyperbilirubinemia in the first 48 h of life. Umbilical cord bilirubin is a poor marker for predicting neonatal infection.

Associations between Gilbert's syndrome and personality characteristics

Abstract Objective Gilbert's syndrome (GS) is a benign genetic disorder that is characterized by intermittent mild jaundice in which the liver doesn't process bilirubin properly. The aim of this study was to determine whether GS patients have a different personality structure and if there are associations between properties of temperament and character and total bilirubin levels. Methods A total of 1665 young male individuals aged from 19 to 30 who were admitted for occupational examinations were included in this study. Careful patient history was taken, a detailed physical examination was conducted, and hematologic and biochemical tests and abdominal ultrasonography were performed. The Turkish version of the Temperament and Character Inventory (TCI) was administered to all participants. 81 patients diagnosed with GS and 150 randomly chosen healthy individuals (control group) were investigated with comparison and correlation analyses. Results GS patients had higher scores than healthy controls for disorderliness (NS4) (p = 0.018), sentimentality (RD1) (p = 0.042), and fatigability (HA4) (p = 0.03). Moreover, Gilbert syndrome patients scored lower than controls for empathy (C2) (p = 0.041) and transpersonal identification (ST2) (p = 0.044). Bilirubin levels were positively associated with disorderliness (NS4) (r = 0.141, p = 0.032) and fatigability (HA4) (r = 0.14, p = 0.033). Conclusions GS patients may have some different personality characteristics from healthy individuals. This study is an initial exploration of the personality structure of GS patients and the findings should be interpreted with caution. Further prospective studies are needed to identify the relationship between Gilbert disease and personality characteristics.

Accuracy of transcutaneous bilirubin measurement in full-term newborns at 3400 meters above sea level / Precisión de la bilirrubinometría transcutánea en recién nacidos a término a 3400 metros sobre el nivel del mar

Abstract Background: Neonatal jaundice is a frequent benign condition in newborns. However, a rapid diagnosis must be established for its most appropriate treatment. The objective of this study was to measure the correlation between total serum bilirubin (TSB) and transcutaneous bilirubin (in forehead and sternum) in full-term newborns at 3400 m above sea level. Methods: We conducted a prospective and cross-sectional study in full-term newborns with clinical jaundice from the Hospital Regional in Cusco-Peru. General characteristics and measurement of TSB, transcutaneous forehead bilirubin (TcBF), and transcutaneous bilirubin in the sternum (TcBS) were explored. Correlation, sensitivity, and specificity were calculated. Receiver operating characteristic (ROC) curves were constructed using the SPSS statistical package, version 22.0. Results: A total of 123 newborns were evaluated. The mean bilirubin values were 13.7 ± 3.5 for TcBF, 14.1 ± 3.1 for TcBS, and 13.8 ± 3.9 for TSB. In addition, Pearson correlation coefficients between TSB/TcBF and TSB/TcBS were 0.90 and 0.91, respectively (p < 0.001). For the percentile 95 cut-off point, a sensitivity of 93% and 100% and a specificity of 89% and 80% were obtained for TcBF and TcBS, respectively, with an area under the curve of 0.813 for TcBF and 0.815 for TcBS (p < 0.001) Conclusions: Measurement of transcutaneous bilirubin is a fast and painless method that can be considered a reliable tool for screening and monitoring neonatal jaundice, but not for a definitive diagnosis to decide the use of phototherapy in full-term newborns at 3400 m above sea level.

Resumen Introducción: La ictericia neonatal es una condición benigna y frecuente en los recién nacidos, en quienes es preciso hacer un diagnóstico rápido para el tratamiento más adecuado. El objetivo de este estudio fue determinar la correlación entre la bilirrubina sérica total (BST) y la bilirrubina transcutánea (frente y esternón) en recién nacidos a término a 3400 metros sobre el nivel del mar. Método: Estudio prospectivo y transversal en recién nacidos con ictericia clínica en el Hospital Regional de la Ciudad de Cusco, Perú. Se exploraron las características generales y se midieron la BST, la bilirrubina transcutánea en la frente (BTcF) y la bilirrubina transcutánea en el esternón (BTcE). Se calcularon la correlación, la sensibilidad y la especificidad, y se elaboraron las curvas de características operativas del receptor (ROC) con el paquete estadístico SPSS 22.0. Resultados: Se evaluaron 123 recién nacidos. El promedio de la BST fue de 13.8 ± 3.9, el de la BTcF fue de 13.7 ± 3.5 y el de la BTcE fue de 14.1 ± 3.1. La correlación entre BST/BTcF y BST/BTcE fue de 0.90 y 0.91, respectivamente (p < 0.001). Para el punto de corte del percentil 95 según el nomograma Bhutani se obtuvo una sensibilidad del 93% y el 100%, y una especificidad del 89% y el 80%, para la BTcF y la BTcE, respectivamente, con un área bajo la curva ROC de 0.813 para la BTcF y de 0.815 para la BTcE (p < 0.001). Conclusiones: La medición de la bilirrubina transcutánea es un método rápido e indoloro, y podría ser considerado confiable para el despistaje y el seguimiento de la ictericia neonatal, mas no para un diagnóstico definitivo con el fin de decidir el uso de fototerapia en recién nacidos a término a 3400 metros sobre el nivel del mar.

Predictores de Coledocolitiasis en pacientes con litiasis vesicular sintomática tratados en la Segunda Cátedra de Clínica Quirúrgica, Hospital de Clínicas, San Lorenzo año 2017-2019 / Predictors of Choledocholithiasis in patients with symptomatic gallstones treated in the II General Surgery Service of Clinica´s Hospital, San Lorenzo, year 2017-2019

La litiasis vesicular sintomática puede presentarse asociada a litiasis de la vía biliar principal, siendo necesaria la utilización de medios diagnósticos adecuados para su posterior tratamiento. En este trabajo, se sugiere la evaluación mediante las guías de la Sociedad Americana para Endoscopia Gastrointestinal (American Society for Gastrointestinal Endoscopy ASGE), usando factores como la edad, pruebas hepáticas y hallazgos ecográficos, categorizando a los pacientes en baja, intermedia y alta probabilidad de coledocolitiasis. Estudio de diseño retrospectivo, observacional, descriptivo, de corte transversal, con un muestreo no probabilístico de casos consecutivos, sobre pacientes con diagnóstico de litiasis vesicular sintomática y sospecha de litiasis de la via biliar principal internados en la II Cátedra de Clínica Quirúrgica, del Hospital de Clínicas de San Lorenzo, entre los años 2017 a 2019. Con los siguientes resultados, de un total de 339 pacientes con diagnóstico de litiasis vesicular sintomática, el 6,64% tuvo el diagnóstico de coledocolitiasis asociada. En cuanto a los predictores muy fuertes de coledocolitiasis el más frecuentemente (68,6%,) encontrado fue el nivel de la bilirrubina total ≥ 4mg/dl; de los predictores fuertes el 70,6% presentaba la vía biliar principal dilatada; de los predictores moderados, el 84,3% presentó las enzimas hepáticas alteradas. En conclusión, se pudo identificar que la mayoría de los pacientes presentó alta probabilidad de coledocolitiasis y la conducta tomada fue realizar en primer lugar una colangiografía retrógrada endoscópica, con fines terapéuticos y luego colecistectomía, correspondiente al manejo correcto establecido por las guías actuales internacionales.

Symptomatic gallstones can occur associated with lithiasis of the main bile duct, requiring the use of adequate diagnostic tools for subsequent treatment. In this paper, we suggest using the guidelines of the American Society for Gastrointestinal Endoscopy (ASGE), that uses factors such as age, liver tests, and ultrasound findings, categorizing patients as those with low, intermediate, and high probability. of choledocholithiasis. A Retrospective, observational, descriptive, cross-sectional design study, with a non-probabilistic sampling of consecutive cases, on patients with a diagnosis of symptomatic gallstones and suspected stones of the main bile duct admitted to the the 2nd Surgical Department and Service of Clinica´s Hospital of San Lorenzo, between the years 2017 to 2019. With the following results; of a total of 339 patients with the diagnosis of symptomatic gallstones, 6.64% had associated choledocholithiasis. Regarding the very strong predictors of choledocholithiasis, the most frequent (68.6%) was the total bilirubin level ≥ 4mg / dl; 70.6% had a dilated main bile duct as a strong predictor; as a moderate predictor, 84.3% had altered liver enzymes. In conclusion, it was possible to identify that most of the patients presented a high probability of choledocholithiasis and the action taken was to first perform an endoscopic retrograde cholangiography, for therapeutic purposes, and then cholecystectomy, corresponding to the correct management established by current international guidelines.

Bilirrubina: mecanismos tóxicos de una molécula antioxidante / Bilirubin: The toxic mechanisms of an antioxidant molecule

La hiperbilirrubinemia es el motivo más frecuente de consulta e internación en el período neonatal. Requiere la instauración oportuna de un tratamiento eficiente, ya que los recién nacidos son especialmente vulnerables a los daños que la bilirrubina puede causar en el sistema nervioso central, debido a características propias de esta etapa de la vida.La bilirrubina en altas concentraciones produce neurotoxicidad y estrés oxidativo. Sin embargo, estudios de biología molecular demuestran que la misma molécula se comporta como un potente antioxidante.El objetivo de esta actualización es revisar cuáles son los procesos por los que la bilirrubina genera daño celular y cuáles son sus efectos antioxidantes beneficiosos. Conocer estos mecanismos facilitaría una indicación más precisa de luminoterapia individualizada, eficaz y oportuna. Hasta nuevos avances científicos, la prescripción de este tratamiento debe ser orientada por consenso de expertos

Hyperbilirubinemia is the most common reason for consultation and hospitalization in the neonatal period. It requires a timely initiation of an effective treatment because newborn infants are especially vulnerable to damage caused by bilirubin in the central nervous system due to the characteristics typical of this stage of life.High bilirubin levels result in neurotoxicity and oxidative stress. However, molecular biology studies have demonstrated that bilirubin itself acts as a potent antioxidant.The objective of this update is to review the processes whereby bilirubin causes cell damage and determine its beneficial antioxidant effects. Knowing these mechanisms may facilitate a more accurate indication of a customized, effective, and timely phototherapy. Until new scientific advances are made, phototherapy should be prescribed based on expert consensus.