Manish Butte

[Differential analysis of gene expression profiles in hepatocellular carcinoma patients with high and low levels of alpha-fetoprotein].

Zhonghua Zhong Liu Za Zhi. 2020 May 23;42(5):396-402

Authors: Wang XJ, Shen RF, Wang X, Wang YR, Xiao T

Abstract
Objective: To investigate the differential gene expression profiles of alpha-fetoprotein (AFP) high- and low-expressing hepatocellular carcinoma (HCC), and to provide a theoretical basis for the molecular mechanism and prognosis analysis of HCC. Methods: The transcriptome data and related clinical information from 368 HCC cases were obtained from the Cancer Gene Atlas (TCGA) public database. The samples were divided into AFP high expression (AFP(high)) group and low expression (AFP(low)) group according to the quartile of AFP mRNA expression, with 92 cases in each group. The differential gene analysis was carried out using the DEseq2 package in the R software. The functional and KEGG pathway enrichment analysis of the differential genes was performed using ClusterProfiler package. The protein-protein interaction network was constructed to screen hub genes using the String database and Cytoscape software. The single-sample GSEA analysis was performed to enrich and score signature gene sets using the GSVA package. And then RNAseq data and real-time quantitative polymerase chain reaction (RT-qPCR) were used for independent dataset validation and tissue validation. Results: The clinical analysis showed that high expression of AFP was significantly associated with poor pathological differentiation and ethnicity (P<0.05 for both). A total of 1 382 differential genes were obtained by bioinformatics analysis, of which 931 genes were up-regulated and 451 genes were down-regulated in AFP(high) group. GO enrichment analysis showed that the highly expressed genes were mainly correlated with the processes of appendage development, limb development, and skeletal system development, while lowly expressed genes were related to metabolic-related processes such as xenobiotic metabolism, steroid metabolism, and cellular response to xenobiotic stimuli. KEGG pathway enrichment analysis revealed that highly expressed genes were mainly involved in primary immunodeficiency, neuroactive ligand-receptor interaction, and cytokine-cytokine receptor interaction, while lowly expressed genes were mainly involved in retinol metabolism, chemical carcinogenesis, steroid hormone biosynthesis and other pathways. A prognostic related gene set that was consisted of AURKB, TTK, CENPA, UBE2C, HJURP, and KIF15 was identified. And the high expression of this gene set was related to the shorter recurrence-free survival and overall survival time in HCC patients, and its enrichment score was positively correlated with AFP expression (r=0.475, P<0.001). The validation results of RNAseq data were basically consistent with the TCGA data. The RT-qPCR results showed that AURKB, KIF15, and UBE2C were significantly overexpressed in HCC tissues with high AFP expression. Although the expression of AURKB, TTK, KIF15, and UBE2C was not related to recurrence-free survival and overall survival of HCC patients, there was a tendency that the patients with high AFP levels showed relatively shorter recurrence-free survival time and overall survival time. Conclusions: There is a large difference in gene expression profiles between AFP(high) and AFP(low) HCC. The prognostic signature may cooperate with AFP to promote the initiation and development of HCC. It also may explain the tumorigenesis in HCC with different AFP levels, and provide new clues for the prognosis of HCC.

PMID: 32482029 [PubMed – in process]

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Gene analysis of seven cases of primary immunodeficiency.

Transl Pediatr. 2020 Apr;9(2):117-125

Authors: Zhu Y, Li L, Mao G, Zhang L, Wang J, Li N

Abstract
Background: Primary immune deficiency diseases (PID) are a group of potentially serious disorders in which inherited defects in the immune system lead to increased infections. This paper explores the clinical characteristics and pathogenic gene mutation of PID.
Methods: The clinical data, clinical manifestations, and gene sequencing results of seven children were analyzed.
Results: Among the seven children, six were male, and one was female, aged from 4 months to 13 years old. All of them had a history of repeated infection and pneumonia. High throughput sequencing (NGS) showed that the BTK gene of case 1 had c.1921c > t mutation; the BTK gene of case 2 had c.906-908del splice site mutation; the BTK gene of case 3 had c.718delg mutation; the cybb gene of case 4 had c.469c > t mutation; the IL2RG gene of case 5 had c.202g > A mutation; the STAT1 gene of case 6 had c.854a > G mutation; the case 7 had c.718delg mutation. There was c.1154c > t mutation in the STAT1 gene. Cases 1, 3, 6 and 7 were new mutations, and cases 2, 4, and 5 were inherited from mothers.
Conclusions: In clinical cases of children with recurrent infection, the immunologic index is abnormal, so we need to be highly aware of the possibility of PID, and timely high-throughput sequencing is helpful for the diagnosis.

PMID: 32477911 [PubMed]

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Case of mucormycosis of mandible after self-extraction of teeth incidentally detected to have chronic granulomatous disease: Case report and literature review.

Med Mycol Case Rep. 2020 Jun;28:55-59

Authors: Agarwal S, Anand A, Ranjan P, Meena VP, Ray A, Dutta R, Jadon RS, Vikram NK

Abstract
Mucormycosis isolated to the mandible is a rare presentation occurring generally after dental procedures. The case we report presented with discharging sinuses over facial region with radiological appearance of isolated osteomyelitis of the mandible. The patient used to apply an addictive dental powder over his teeth leading to caries. Following this, he pulled out all his teeth, which probably led to his condition. Invasive sampling revealed mucormycosis. An extensive search for an underlying immunodeficiency revealed that the patient had chronic granulomatous disease (CGD). Despite a prolonged course of L-Amphotericin B, the patient continued to have intermittent pus discharge and surgical debridement and curettage was eventually required. The patient had a chronic course with minimal soft tissue involvement which initially did not raise the suspicion of mucormycosis. The main learning point is that an unusual invasive fungal infection in an otherwise healthy host can be the first symptom of an underlying primary immunodeficiency, like CGD. Invasive fungal infections in patients with CGD often have an indolent course.

PMID: 32477856 [PubMed]

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Primary Immunodeficiencies in a Mesoregion of São Paulo, Brazil: Epidemiologic, Clinical, and Geospatial Approach.

Front Immunol. 2020;11:862

Authors: Boton Pereira DH, Primo LS, Pelizari G, Flores E, de Moraes-Vasconcelos D, Condino-Neto A, Prestes-Carneiro LE

Abstract
Background: Primary immunodeficiencies (PIDs) are rare genetic disorders leading to immunologic abnormalities that can affect different organs and systems. We determined the epidemiology, clinical, and geospatial characteristics of PID disorders among patients diagnosed over a 5 year period in a reference hospital covering a mesoregion in São Paulo, Brazil. Methods: A retrospective analysis of 39 patients with recognizable PIDs according to the criteria of the European Society of Primary Immunodeficiencies were enrolled. Thirty-four patients came from outpatient immunodeficiency clinics and five patients from active search. Demographic, clinical, and immunologic data were collected, and maps were constructed using a geographic information system. Results: The ratio of females to males was 1.4:1, and 48.7% of patients were younger than 17 years of age. The mean age at the onset of symptoms in children was 2.0 years [standard error of the mean (SEM), 1.7 years] and the diagnosis lag was 5.1 years (SEM, 3.1 years); the mean age at diagnosis in adults was 16.3 years (SEM, 11.8 years) and the lag was 10.8 years (SEM, 10.9 years). Antibody deficiency and common variable immunodeficiencies were the most common categories and phenotypes, respectively. The need for intravenous antibiotics and respiratory tract infections were the most prevalent warning signs, with an overall mortality rate of 15.3%. Autoimmune diseases were diagnosed in 56.4% and visceral leishmaniasis in 5.1% of patients. In the active search, 29 patients were investigated and 17.2% were diagnosed; early diagnosis, the involvement of multidisciplinary professionals, and dissemination of knowledge achieved milestone benefits. The distribution of PID networks in Brazil shows great asymmetry between regions and at a regional level; it was shown that the patients lived mainly in Presidente Prudente municipality. Conclusions: The implementation of an immunodeficiency outpatient clinic in a referral hospital covering a mesoregion with a large population has led to the generation of policies and practices to improve the diagnosis, quality of life, and care of patients with PIDs and their families. Furthermore, the search for hospitalized patients with warning signs for PIDs showed great benefits. Inequality in the distribution of PID network centers in Brazil was demonstrated.

PMID: 32477349 [PubMed – in process]

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Identifying Novel Mutations in Iranian Patients with LPS-responsive Beige-like Anchor Protein (LRBA) Deficiency.

Immunol Invest. 2020 Jun 01;:1-7

Authors: Ghaini M, Arzanian MT, Shamsian BS, Sadr S, Rohani P, Keramatipour M, Mesdaghi M, Eskandarzadeh S, Lo B, Jamee M, Chavoshzadeh Z

Abstract
LPS-responsive beige-like anchor protein (LRBA) deficiency is a monogenic primary immunodeficiency characterized by a heterogeneous spectrum of clinical manifestations associated with immune dysregulation. In this study, we reported clinical, immunologic, and genetic evaluation of two Iranian patients from unrelated families, both suffering from recurrent respiratory tract infections, failure to thrive, interstitial lung disease, autoimmune cytopenia, and hypogammaglobulinemia. Pulmonary abscess in one patient and persistent enteropathy in another were also observed. Further investigations revealed causative mutations in the exon (c.2166_2766del) and intron (c.4730-3 T > G) of the LRBA gene. These results may provide further elucidation of the clinical phenotypes and responsible genetic factors of LRBA deficiency.

PMID: 32476511 [PubMed – as supplied by publisher]

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PHYSICIAN CHARACTERISTICS THAT INFLUENCE PATIENT PARTICIPATION IN THE TREATMENT OF PRIMARY IMMUNODEFICIENCY.

Patient Educ Couns. 2020 May 19;:

Authors: Lamb CC, Wang Y

Abstract
OBJECTIVE: Shared decision making (SDM) is recommended to improve healthcare quality. Physicians who use a rational decision-making style and patient-centric approach are more likely to incorporate SDM into clinical practice. This paper explores how certain physician characteristics such as gender, age, race, experience, and specialty explain patient participation.
METHODS: A multi-group structural equation model tested the relationship between physician decision-making styles, patient-centered care, physician characteristics, and patient participation in clinical treatment decisions. A survey was completed by 330 physicians who treat primary immunodeficiency. Sample group responses were compared between groups across specialty, age, race, experience, or gender.
RESULTS: A patient-centric approach was the main factor that encouraged SDM independent of physician decision-making style with both treatment protocols and product choices. The positive effect of patient-centrism is stronger for immunologists, more experienced physicians, or male physicians. A rational decision-making style increases participation for non-immunologists, older physicians, white physicians, less-experienced physicians and female physicians.
CONCLUSION: A patient-centric approach, rational decision-making and certain physician characteristics help explain patient participation in clinical decisions. Practice Implications Future SDM research and policy initiatives should focus on physician adoption of patient-centric approaches to chronic care diseases and the potential bias associated with physician characteristics and decision-making style.

PMID: 32475713 [PubMed – as supplied by publisher]

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