Debates on the natural history of chronic hepatitis B virus infection during the update of Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version) / 临床肝胆病杂志

This article introduces the debates on the natural history of chronic hepatitis B virus (HBV) infection during the update of Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version), including nomenclature and definition, HBV infection, HBV DNA threshold for patients in the immune-tolerant phase, indeterminate phase and natural history, clinical diagnosis and natural history, and HBV DNA threshold for patients in the inactive phase.

Research Progress on Gene Mutation and CHIP in Pathogenesis of MDS --Review / 中国实验血液学杂志

With the development of molecular biology techniques, the people's understanding of myelodysplastic syndromes (MDS) has greatly improved, a heterogeneous hematopoietic pre-malignant disorder of the stem cells. Gene mutations include RNA splicing, DNA methylation, chromosome modification, transcription factors, signal transduction kinases, RAS pathways, cohesion complexes, DNA repair, etc. Gene mutation is the determinant of diagnostic typing and therapeutic efficacy of MDS. The new concepts of CHIP and ICUS have aroused people's attention to the elderly patients with clonal hematopoiesis and non-clonal cytopenia but without MDS characteristics, who have the possibility of high-risk transformation to MDS and leukemia. In order to better understand the pathogenesis of MDS, the significance of gene mutations, CHIP and ICUS in the diagnosis and prognosis of MDS were reviewed in this paper.

Stratifying indeterminate cytology thyroid nodules by combining Thyroid Imaging Reporting and Data Systems (TI-RADS) and The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)

Objective@#To determine the risk of malignancy of Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) indeterminate Thyroid Nodules (Bethesda III, IV and V) by combining cytologic (TSBRTC) and Thyroid Imaging Reporting and Data Systems (TI-RADS) ultrasonographic features based on final histopathology.@*Methods@#Design: Retrospective review of records. Setting: Tertiary Private Training Hospital. Participants: 551 records. @*Results@#Among 81 eligible participants, 59 out of 84 nodules (70.24%) wer malignant on histopathology. The malignancy risk of Bethesda classification was 60.87% (28 out of 46) for Bethesda III, 57.14% (8 out of 14) for Bethesda IV and 95.83% for Bethesda V. The malignancy risk for TI-RADS categories was 0 % (0/1) for TI-RADS 2, 50% (10 out of 20) for TI-RADS 3, 71.05 % for TI-RADS 4 and 91.67 % for TI-RADS 5. The highest risk of malignancy (100%) was associated with [Bethesda IV/TI-RADS 1, 2, and 3], [Bethesda V/TI-RADS 1, 2 and 3 [Bethesda IV and V/TI-RADS 1, 2 and 3] and [Bethesda IV/TI-RADS 5]. The lowest risk of malignancy (33.33%) was associated with [Bethesda III/TI-RADS1, 2 and 3]. A high Bethesda classification (Bethesda V) was almost 5x more likely to have a malignant anatomorphology compared with Bethesda III (p = .05) while a TI-RADS 4 or 5 category was almost 5x more likely to have a malignant anatomorphology compared to TI-RADS 1, 2 or 3 (p = .026).@*Conclusion@#This study showed that TI-RADS scoring is a sensitive diagnostic classification in recognizing patients with thyroid cancer and combining Bethesda classification and TI-RADS scoring increases the sensitivity in the diagnosis of malignant thyroid nodules. A higher likelihood of malignancy is associated with higher Bethesda classification and TI-RADS scoring.

Further discussion on the antiviral treatment of chronic hepatitis B patients with indeterminate phase / 临床肝胆病杂志

This paper discusses further on the antiviral treatment of chronic hepatitis B patients with indeterminate phase. These patients have a high proportion of significant necroinflammation and fibrosis in the liver， and a higher risk of disease progression compared with those with true HBeAg－positive chronic hepatitis B virus （HBV） infection （formerly called the immune tolerance phase） or HBeAg－negative chronic HBV infection （formerly called the immune control phase）. Antiviral therapy may reduce the risk of HBV－related hepatocellular carcinoma in chronic hepatitis B patients with indeterminate phase.

Clonal hematopoiesis of indeterminate potential and aging / 中华老年医学杂志

Clonal hematopoiesis with indeterminant potential(CHIP)is defined as the proportion of detectable clonal hematopoietic cells in peripheral blood exceeding 2% and without confirmed hematologic malignancy.CHIP could increase the risk of malignant diseases through changes in DNA damage response, transcriptional programming and epigenetic modification.The incidence of malignant tumors in the blood system is significantly higher in the CHIP patients than healthy person.In addition, CHIP represents a negative factor associated with aging.Recent studies have found that the incidences of infections, anemia, heart failure, thrombotic events, and tumors of the blood system in CHIP carriers were significantly increased.Starting with the epigenetic modifications, phenotypic changes and inflammatory mechanisms of CHIP-related gene mutations, this paper discussed the mechanisms of CHIP-related diseases and possible intervention aimed at aging.

Follow-up study of cases with indeterminate HIV antibody immunoblotting test results / 公共卫生与预防医学

Objective To study the characteristics and follow-up results of 94 people with indeterminate Western blot (WB) results of HIV antibody. Methods A retrospective analysis was conducted on the characteristics and outcome of 94 patients with indeterminate WB results of HIV antibody from AIDS confirmation laboratories in Jiading District from 2016 to 2019. Results The 94 subjects came mainly from clinical diagnostic tests, accounting for 68.09% of the total, followed by counseling tests and maternal examinations, accounting for 12.77% and 10.64%，respectively. Follow-up testing was performed on 48 patients with indeterminate HIV antibodies, with a follow-up detection rate of 51.06%. Among them, 25.00% turned positive during the follow-up, and 39.58% turned negative. There was no significant difference in the follow-up rate between different population groups and WB band-types. The positive conversion rate of counseling test samples was the highest, accounting for 55.56% of all positive conversion cases. There was a total of 14 WB band types, mainly in p24, gpl60 and p24pl60, accounting for 54.26%, 17.02% and 9.57%, respectively. There was a significant difference in the positive conversion rate of antibodies with different patterns of WB bands. The positive conversion rate of WB band type gp160gp41p24 was 100%, while the positive rate of gp160p24, gp160, and p24 was 66.67%, 37.5% and 11.54%, respectively. Conclusion The samples with indeterminate WB results of HIV antibody were mainly from medical institutions, and the follow-up retest rate was low. Follow-up tests of specific populations and samples with specific patterns of WB bands should be strengthened to confirm HIV infection status as soon as possible.

Should chronic hepatitis B in the indeterminate phase be treated？ / 临床肝胆病杂志

This article discusses the definition of the indeterminate phase of chronic hepatitis B and summarizes the proportion of patients in the indeterminate phase of chronic hepatitis B among patients with chronic HBV infection, as well as their risk of hepatocellular carcinoma and related treatment recommendations.

Epidemiological investigation and follow-up study of indeterminate HIV antibody test results in Jiading, Shanghai / 上海预防医学

Objective To investigate the rate and the population distribution of subjects with indeterminate result of HIV antibody test and to understand the relationships between the western blot(WB)banding patterns and HIV infection through follow-up reexamination. Methods Samples with indeterminate results of HIV antibody test were collected by Jiading Center for Disease Control and Prevention from 2013 to 2017. They were used for analysis of the source, the distribution of Western blotting band pattern and the follow-up results. Results Among 698 samples required to be re-tested for confirmation of HIV infection, 151(21.63%)showed indeterminate WB test results. There were 18 types of WB band in 151 HIV antibody-indeterminate samples. The most common band types, accounting for 79.47%, were p24, gp160, and gp160p24. One hundred(among 151)subjects were followed up and the success follow-up rate was 50.00%. Among them, 28(56.00%)samples were still with indeterminate results of HIV antibody, 11(22.00% turned to be negative and 11(22.00%)turned to positive. The follow-up confirmatory tests showed that 67.86% of the samples with p24 band were still with indeterminate results and 40.00% of the samples with gp160 band became HIV antibody-negative. The samples with one of the three band patterns of gp160gp120p24, gp160p24p17 and gp160gp120p66p51 all became HIV antibody-positive. Conclusion The detection rate of indeterminate HIV antibody results varies in different populations. Positive conversion rates with different WB band patterns are different. Follow-up of the populations with specific WB band patterns should be strengthened to detect HIV infection cases as early as possible.

Indeterminate form of Chagas disease: historical, conceptual, clinical, and prognostic aspects

Abstract Chagas disease (CD) remains a serious endemic disease in Latin America and a major public health problem. Because of globalization, the disease has spread to non-endemic areas in the northern hemisphere. In the chronic phase of the disease, most patients present with the indeterminate form (IF), characterized by positive serology for Trypanosoma cruzi, absence of clinical findings, and normal findings in electrocardiogram (ECG). IF was not recognized as a clinical entity until decades after the discovery of the disease, and only in the 1940-50s, it was categorized as a form of CD, and its conceptual definition was ratified in the 1980s. Children, adolescents, and young adults with the IF benefit from etiological treatment and tend to have less progression to heart disease in the long term than the untreated ones. IF patients have an essentially benign clinical condition, and their prognosis can be compared to that of healthy individuals with normal ECG findings. Currently, because of aging, patients with the IF have comorbidities that require attention in health services.

Are the anatomical, clinical, and ultrasound characteristics of thyroid nodules with Bethesda III or IV cytology and ACR TI-RADS 3, 4, or 5 able to refine the indications for molecular diagnostic tests?

ABSTRACT Objective: To analyze the association of clinical, anatomical, and ultrasound (US) characteristics of malignancies in Bethesda III or IV (III-B or IV-B) thyroid nodules. Subjects and methods: The association between malignancies and the following variables were analyzed: III-B or IV-B, age < 55 years and ≥ 55 years, sex, family history of thyroid cancer, history of irradiation, nodule size, and ACR TI-RADS classification in 62 participants who underwent thyroidectomy. Results: Of the 62 participants, 87.1% (54/62) were women, 74.2% were < 55 years old, 95.2% had no family history of thyroid cancer, 56.5% had nodules < 2 cm in size, 62.9% were IV-B, and 69.4% were ACR TI-RADS 4. Thirty-two patients had thyroid carcinoma, and 30 had benign histology. Among all factors associated with malignancy, only ACR TI-RADS 5 classification on US was found to be statistically significant (p = 0.014), while III-B with architectural atypia cytological classification was the only one significantly associated with benign status (p = 0.004). Conclusion: Only a high risk of malignancy as assessed using US was able to refine the indication for molecular tests in a group of patients with indeterminate nodules. We found 85% (53/62) of III-B or IV-B thyroid nodules would benefit from available molecular diagnostic tests.

Epidemiological profile of inflammatory bowel disease in Caxias do Sul, Brazil: a cross-sectional study

ABSTRACT BACKGROUND: Inflammatory bowel diseases affect mostly young patients and have a huge impact on their quality of life and growing treatment costs. Currently, there are few Brazilian studies concerning their epidemiological profile. OBJECTIVE: The aim of this study was to describe the regional clinical and epidemiological profile of these pathological conditions in Caxias do Sul, Brazil. DESIGN AND SETTING: Cross-sectional study in Caxias do Sul (RS), Brazil. METHODS: A search for patients was conducted in the municipality's special medications pharmacy using the International Classification of Diseases, and medical records were manually reviewed for data collection. Sixty-seven patients were included. RESULTS: The patients' mean age was 46.5 years and females predominated (71.6%). Ulcerative colitis was the most prevalent disease (70%) and Montreal E3 was the most prevalent presentation. The mean age at diagnosis was 39 years. Most patients had recently undergone colonoscopy (67%). Only five patients (7.4%) had records of hospital admission due to the disease, while 12 (18%) underwent a surgical procedure during follow-up. Sixty patients (89.5%) were using aminosalicylates, while less than one fifth were using immunosuppressants or immunobiological drugs: 19.4% and 14.9%, respectively. CONCLUSION: The profile of inflammatory bowel disease patients in this region of Brazil is similar in some characteristics to other published Brazilian data, although it differs in others such as higher frequency of pancolitis. A prospective study on these patients is planned in this region, in order to improve the data quality.

Clinical profile and outcome of patients with indeterminate acute liver failure

Background: Acute liver failure (ALF) is a rare medical emergency and devastating clinical syndrome associated with high mortality. Indeterminate ALF still forms a significant number of cases in India as well in the world. We aimed to determine the clinical profile and outcome of patients with indeterminate ALF.Methods: A total of 30 patients with a diagnosis of Indeterminate ALF were included in the study. The variables evaluated were demographic, signs and symptoms, biochemical parameters, severity of liver injury, outcome, complications and duration of hospital stay.Results: Overall mortality was 18 (60%). Majority of the patients were females (56.7%). Majority of patients (60%) had grade III and IV encephalopathy at the time of admission. The mean age in Survived group was 30.6±11.6 years and in Died group was 42.6±10.2 years (p=0.005). INR, bilirubin AST, ALT and creatinine were significantly higher in Died group than Survived group. Mean grade of coma was significantly higher in Died group than Survived group (p=0.010). MELD Score was significantly higher in Died group 35.8±6.7 than Survived group 27.5±5.8 (P = 0.001). Sepsis and renal failure occurred more frequently in Died group. Duration of hospital stay was also significantly more in Died group versus Survived group (p=0.003).Conclusions: Indeterminate ALF disproportionately affected young females. Mortality was as high as 60%. The marked difference in spontaneous survival can be explained by the severity of hepatic dysfunction on admission and more frequent complications.

SPECT-CT in Differentiating Metastatic and Degenerative Lesions of the Spine

@#Introduction: The purpose of this study was to determine the usefulness of SPECT-CT in differentiating metastatic and degenerative disease of the spine. Methods: Twenty-eight patients aged 50 years and above diagnosed with various cancers were referred for whole body (WB) planar bone scintigraphy. Those with a maximum three foci of tracer uptake in the spine were selected for the study. SPECT-CT of these areas of uptake was performed and the lesions were classified as degenerative, indeterminate or metastasis. A repeat study (WB planar bone scintigraphy and SPECT-CT) was performed between 3 to 12 months later. These areas of uptake were reassessed and compared with the first WB planar bone scintigraphy and SPECT-CT. The second SPECT-CT was used as the standard for the diagnosis. Results: Thirty-seven lesions in 28 patients were assessed. The sensitivity of the first WB planar bone scintigraphy, second WB planar bone scintigraphy and first SPECT-CT is 75%, 62.5% and 75% respectively. The specificity of the first WB planar bone scintigraphy, second WB planar bone scintigraphy and first SPECT-CT is 86%, 93%, 90% respectively. There was 2.7% of ‘indeterminate lesion’ in the first WB planar bone scintigraphy, 5.4% in the second WB planar bone scintigraphy, and 5.4% in the first SPECT-CT. The indeterminate lesions were resolved in the second SPECT-CT. Conclusion: SPECT- CT is useful in differentiating degenerative disease from metastatic lesions in the spine.

Use of tissue doppler imaging for the early detection of myocardial dysfunction in patients with the indeterminate form of Chagas disease

Abstract INTRODUCTION: Chagas disease is one of the most common diseases in Latin America and heart involvement is the main cause of death. This study aimed to determine differences in tissue Doppler imaging (TDI) parameters in the assessment left and right ventricular function in patients with the indeterminate form of Chagas disease compared to those in healthy controls. METHODS: We compared 194 patients with the indeterminate form of Chagas disease to 72 age-matched healthy individuals. We considered p-values <0.05 to be statistically significant. RESULTS: TDI analysis of the right ventricular (RV) showed lengthened isovolumic relaxation time (IRT) and higher RV index of myocardial performance (RIMP) and left ventricle (LV) index of myocardial performance (LIMP) in the Chagas group than in the control group, indicating RV and LV systolic and diastolic myocardial damage. TDI analysis of the myocardial velocities of the interventricular septum and the lateral wall of the LV also showed a systolic and diastolic myocardial damage. CONCLUSIONS: The study results demonstrated early LV systolic and diastolic myocardial damage in the RV and LV in patients with the indeterminate form of Chagas disease by TDI. These early findings of RV and LV dysfunction may help identify patients who will progress to heart failure during the disease course. TDI should be included in initial patient evaluations because it allows adequate follow-up and treatment.

Utilidad de los marcadores moleculares en el diagnóstico de nódulos tiroideos con citología indeterminada

RESUMEN Los nódulos tiroideos representan un problema clínico a nivel mundial debida a su alta prevalencia. La importancia clínica de su estudio radica en excluir malignidad, que ocurre entre el 7-15% de los mismos. El método estándar de oro para el diagnóstico de los mismos es el análisis citológico de la punción aspiración con aguja fina. Sin embargo, hasta un 30% de estos presentan citologías indeterminadas (Bethesda III o IV). Con un resultado histopatológico benigno en, aproximadamente tres de cada cuatro de estos casos, la cirugía diagnóstica (tiroidectomía parcial o lobectomía) resulta en un inconveniente ya que expone al paciente a innecesarios riesgos quirúrgicos. En el caso de lesiones malignas, una tiroidectomía en una segunda etapa es a menudo indicada, lo que se asocia con costos adicionales y mayores riesgos de complicaciones quirúrgicas. Es por esto que se requiere de una herramienta con mayor precisión para determinar la benignidad o malignidad de un nódulo tiroideo con citología indeterminada. En este contexto el análisis molecular del tejido tiroideo se convierte en un poderoso complemento para el diagnóstico preoperatorio de los nódulos tiroideos con citología indeterminada, ya que entre el 60 al 70% de los cánceres de tiroides albergan al menos una mutación genética conocida.

ABSTRACT Thyroid nodules represent a clinical problem worldwide due to its high prevalence. The clinical importance lies in excluding malignancy, which occurs between 7-15% of them. The cytological analysis is the gold standard for the diagnosis. However, up to 30% of these have indeterminate cytologies (Bethesda III or IV). In these patients, diagnostic surgeries are performed. With a benign histopathological result in approximately three out of four of these cases, surgery results in an inconvenience since it exposes the patient to unnecessary surgical risks. In the case of malignant lesions, a thyroidectomy in a second stage is often indicated, which is associated with additional costs and increased risks of surgical complications. A more precise method is needed to determine the benignity or malignancy of a thyroid nodule with indeterminate cytology. In this context, molecular analysis of thyroid tissue becomes a powerful complement for the preoperative diagnosis of thyroid nodules with indeterminate cytology, since between 60 to 70% of thyroid cancers harbor at least one known genetic mutation.

Molecular Testing of Thyroid Indeterminate Nodules for Clinical Management Decision

Thyroid nodules are the most common endocrine tumor. Ultrasonography and fine-needle aspiration (FNA) are currently accurate diagnostic tools for evaluating thyroid nodules. However, 10–30% of FNA specimens are cytologically indeterminate. Making an accurate diagnosis between benign and malignant nodules is important so that patients with malignant nodule receive proper treatment and patients with benign nodule can avoid unnecessary treatment. Several genetic changes such as point mutations of the BRAF or RAS and rearrangements of the RET/PTC1, RET/PTC3, PAX8/PPARY are used to adjust to indeterminate FNA. Such a mutational analysis has an excellent positive predictive value (PPV), but there is a weakness in the low negative predictive value (NPV). Gene-expression classifier (GEC) has been found helpful in identify nodules that are benign rather than malignant. GEC has an excellent NPV, but there is a weakness of low PPV. Multiplatform mutational and miRNA test (MPT) and next-generation sequencing assay (NGS) are being studied to compensate for these weaknesses. Molecular tests appear to be a good solution for improving the accuracy of indeterminate FNA cytology specimens and support the clinical management decisions in patients with indeterminate cytologic nodules, but further prospective multicenter trials are required for validation of reported findings and need evaluation of cost-effectiveness. This paper will review recently available molecular diagnostic tools of thyroid nodule.

Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis

The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy.

The BRAFV600E mutation improve diagnostic sensitivity of thyroid nodules with benign or indeterminate cytology results / 中华内分泌外科杂志

Objective@#To investigate the role of BRAFV600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results.@*Methods@#This study included 9837 patients who underwent US-FNA. We mainly analyzed 239 cases with benign or indeterminate cytology, but having a detection of BRAFV600E mutation. BRAFV600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction.@*Results@#In 93 nodules with benign cytology results but positive BRAFV600E mutation, 84 nodules were malignant. Based on the results, US-FNA combined with BRAFV600E mutation analysis will improve sensitivity (Se=94.03%) and negative predictive value (NPV=2.69%) of the thyroid nodules diagnosis than using US-FNA alone (Se=71.03%, NPV=20.76%) .@*Conclusion@#BRAFV600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV. When facing patients with benign or indeterminate cytology but positive BRAFV600E mutation, thyroidectomy should be considered.

The BRAFV600E mutation improve diagnostic sensitivity of thyroid nodules with benign or indeterminate cytology results / 中华内分泌外科杂志

Objective To investigate the role of BRAFV600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results. Methods This study included 9837 patients who underwent US-FNA. We mainly analyzed 239 cases with benign or indeterminate cytology, but having a detection of BRAFV600E muta-tion. BRAFV600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction. Results In 93 nodules with benign cytology results but positive BRAFV600E mutation, 84 nodules were malignant. Based on the results, US-FNA combined with BRAFV600E mutation analysis will improve sensitivity (Se=94.03％)and negative predictive value (NPV=2.69％) of the thyroid nodules diagnosis than using US-FNA alone(Se=71.03％, NPV=20.76％). Conclusion BRAFV600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV. When facing patients with benign or indeterminate cytology but positive BRAFV600E mutation, thyroidectomy should be considered.

Progress of clonal hematopoiesis of indeterminate potential / 白血病·淋巴瘤

Clonal hematopoiesis is a common aging_associated biological state. The incidence of malignant neoplasms for the patients with clonal hematopoiesis of indeterminate potential (CHIP) is 0.5%-1% every year. Potential factors of clonal progression in hematopoietic cells have been summarized, including disordered endogenous immunity caused by the augmentation of proliferative pressure, chromosomal instability caused by telomeres short; the amplification of clonal stem cells, acquisition of new mutations, and aging_associated changes in hematopoietic stem cells, including altered DNA damage response, an altered transcriptional program and epigenetic alterations while failing to support healthy hematopoiesis. CHIP is a vascular risk factor driven by interactions between clonal monocytes_macrophages and the endothelium, as well as a neoplastic progression risk factor driven by the acquisition of additional somatic mutations in the context of many other influences on hematopoiesis and clonal balance. Strategies to reduce the clonal burden associated with CHIP and to inhibit the key inflammatory pathways leading to atherosclerosis could improve the prognosis of the patients.