Analysis on the pathogenic genes of 60 Chinese children with congenital hyperinsulinemia

This study aims to summarize and analyze the clinical manifestations, genetic characteristics, treatment modalities and long-term prognosis of congenital hyperinsulinemia (CHI) in Chinese children. Sixty children with CHI, who were treated at Beijing Children’s Hospital from January 2014 to August 2017, and their families, were selected as subjects. The CHI-related causative genes in children were sequenced and analyzed using second-generation sequencing technology. Furthermore, the genetic pathogenesis and clinical characteristics of Chinese children with CHI were explored. Among the 60 CHI children, 27 children (27/60, 45%) carried known CHI-related gene mutations: 16 children (26.7%) carried ABCC8 gene mutations, seven children (11.7%) carried GLUD1 gene mutations, one child carried GCK gene mutations, two children carried HNF4α gene mutations and one child carried HADH gene mutations. In these 60 patients, eight patients underwent 18F-L-DOPA PET scan for the pancreas, and five children were found to be focal type. The treatment of diazoxide was ineffective in these five patients, and hypoglycemia could be controlled after receiving partial pancreatectomy. In conclusion, ABCC8 gene mutation is the most common cause of CHI in Chinese children. The early genetic analysis of children’s families has an important guiding significance for treatment planning and prognosis assessment.

Download Full-text

Analysis of clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia that is spontaneously relieved

Endocrine ◽

10.1007/s12020-020-02585-x ◽

2021 ◽

Author(s):

Zi-di Xu ◽

Pei-pei Hui ◽

Wei Zhang ◽

Qiao Zeng ◽

Lin Zhang ◽

...

Keyword(s):

Birth Weight ◽

Mutation Analysis ◽

Age Of Onset ◽

Gene Mutations ◽

Spontaneous Remission ◽

Effective Rate ◽

Chinese Children ◽

Genetic Characteristics ◽

Number Of Children ◽

Pathogenic Genes

Abstract Objective This study aimed to analyze the clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia (CHI) that is spontaneously relieved. Methods The patient group comprised 200 children with CHI that were treated at the Beijing Children’s Hospital from January 2006 to December 2018. The patients were divided into two groups according to their prognosis: the spontaneous remission group (n = 92) and the nonspontaneous remission group (n = 108). The clinical characteristics, pathogenic genes, diagnosis and treatment process, and follow-up data of both groups were analyzed retrospectively. Results Of the 200 children with CHI, 92 achieved spontaneous remission. The age of spontaneous remission was between one month and nine years, and 47 of the children were relieved before the age of one year. The median age of onset was 85 days (range: 1–2825 days) in the spontaneous remission group and 2 days (range: 1–210 days) in the nonspontaneous remission group (P < 0.05). The mean birth weight was 3.44 ± 0.76 kg for the spontaneous remission group and 3.95 ± 0.75 kg for the nonspontaneous remission group (P < 0.05). Of the 92 children in the spontaneous remission group, 65 were treated with diazoxide with effective rate of 81.5% (53/65). In 12 cases in which diazoxide treatment failed, octreotide was used with an effective rate of 83.3% (10/12). Of the 108 children in the nonspontaneous remission group, 88 were treated with diazoxide with an effective rate of 43.2 % (38/88), and 29 children were treated with octreotide with an effective rate of 48.28% (14/29). Of the 30 children in the spontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 10 children (10/30, 33.3%) carried mutations. Of the 48 children in the nonspontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 37 children (37/48, 77.1%) were found to carry mutations. All of the differences in the indices mentioned above were statistically significant. Conclusions The rate of spontaneous remission of CHI was significantly higher in children with late age of CHI onset, light birth weight, effective diazoxide treatment, and no common pathogenic gene mutations. Spontaneous remission was also possible for a small number of children that carried mutations in the ABCC and KCNJ11 genes and in whom diazoxide treatment failed.

Download Full-text

Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea

Scientific Reports ◽

10.1038/s41598-021-87718-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeong-Seon Lee ◽

Joong-Gon Kim ◽

Soyoung Lee

Keyword(s):

Polyarteritis Nodosa ◽

Clinical Manifestations ◽

Long Term Outcomes ◽

Childhood Onset ◽

Laboratory Findings ◽

Clinical Presentations ◽

Long Term Prognosis ◽

Digital Amputation

AbstractChildhood-onset polyarteritis nodosa (PAN) is a rare and systemic necrotising vasculitis in children affecting small- to medium-sized arteries. To date, there have been only a few reports because of its rarity. Thus, we aimed to investigate the clinical manifestations, laboratory findings, treatment, and long-term outcomes in patients with childhood-onset PAN and to evaluate the usefulness of the paediatric vasculitis activity score (PVAS). We retrospectively analysed the data of nine patients with childhood-onset PAN from March 2003 to February 2020. The median ages at symptom onset, diagnosis, and follow-up duration were 7.6 (3–17.5), 7.7 (3.5–17.6), and 7.0 (1.6–16.3) years, respectively. All patients had constitutional symptoms and skin manifestations, while five exhibited Raynaud’s phenomenon. Organ involvement was observed in one patient. The median PVAS at diagnosis was 7 (range: 2–32). Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived, but three patients with high PVAS at diagnosis experienced irreversible sequelae, including intracranial haemorrhage and digital amputation. In conclusion, early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. This study suggests that high PVAS score at diagnosis may be associated with poor prognosis.

Download Full-text

4-Jahres-Update der Murano-Studie bestätigt den Stellenwert von Venetoclax in der 2. Therapielinie der CLL

Karger Kompass Onkologie ◽

10.1159/000517067 ◽

2021 ◽

pp. 77-79

Author(s):

Maximilian Schmutz ◽

Sebastian Sommer

Keyword(s):

Response Rate ◽

Residual Disease ◽

Gene Mutations ◽

Progression Free Survival ◽

Lymphocytic Leukemia ◽

Fixed Duration ◽

Genetic Characteristics ◽

Genomic Complexity ◽

End Of Treatment

Purpose: In previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival (PFS) compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics. Patients and methods: Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed. Results: Of 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC (P = 0.042); higher GC was associated with shorter PFS. Higher MRD positivity rates were seen with BIRC3 and BRAF mutations at EOCT and with TP53, NOTCH1, XPO1, and BRAF mutations at EOT. Conclusion: Efficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS. Trial registration: ClinicalTrials.gov NCT02005471.

Download Full-text

Clinical and pathogenetic features of myocardial infarction in patients with atrial fibrillation

Siberian medical review ◽

10.20333/2500136-2020-5-31-39 ◽

2020 ◽

pp. 31-39

Author(s):

S.Y. Borodashkina ◽

◽

K.V. Protasov ◽

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Observational Studies ◽

Risk Group ◽

Clinical Manifestations ◽

High Risk Group ◽

Short Term ◽

Invasive Treatment ◽

Long Term Prognosis

Patients with myocardial infarction (MI) and atrial fibrillation (AF), the number of which is progressively increasing every year, make up a high-risk group for both recurrent cardiovascular events and bleeding; they require special attention from clinicians. The literature review provides data on features of pathogenesis and clinical manifestations of MI in patients with AF. The analysis of data on AF effect observational studies on short-term and long-term prognosis in patients with myocardial infarction was carried out. Mechanisms of occurrence, clinical features and prognostic value of postinfarction AF are considered. From the standpoint of modern clinical guidelines, information is presented on features of MI invasive treatment in combination with AF. Algorithms of anticoagulant and antiarrhythmic therapy in patients of this category are considered.

Download Full-text

Clinical manifestations of acute Coxsackie-B viral myocarditis and pericarditis with a special reference to serum enzyme patterns and long-term prognosis.

The Kurume Medical Journal ◽

10.2739/kurumemedj.34.19 ◽

1987 ◽

Vol 34 (1) ◽

pp. 19-27 ◽

Cited By ~ 5

Author(s):

RYUICHI HASHIMOTO ◽

MASAHIKO OGATA ◽

YOSHINORI KOGA ◽

HIRONORI TOSHIMA

Keyword(s):

Special Reference ◽

Viral Myocarditis ◽

Clinical Manifestations ◽

Serum Enzyme ◽

Long Term Prognosis ◽

Enzyme Patterns ◽

Coxsackie B

Download Full-text

Hemophagocytic Lymphohistiocytosis: A Life Threatening Cytopenic Condition

Faridpur Medical College Journal ◽

10.3329/fmcj.v15i2.53897 ◽

2021 ◽

Vol 15 (2) ◽

pp. 98-102

Author(s):

Suranjit Kumar Saha ◽

MM Shahin Ul Islam ◽

Nasir Uddin Ahmed ◽

Prativa Saha

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Clinical Manifestations ◽

Specific Treatment ◽

Gene Mutations ◽

Multiple Organ ◽

Treatment Modalities ◽

Hematopoietic Stem ◽

Organ Systems ◽

Life Threatening ◽

Poor Outcomes

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder that occurs in many underlying conditions in all age. This is characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells and macrophages resulting in raised cytokine level. Those cytokines and immune mediated injury occur in multiple organ systems. It may be primary and secondary. Primary HLH is familial, childhood presentation and associated with gene mutations. Secondary HLH is acquired, adulthood presentation that occurs in infections, malignancies inflammatory and autoimmune diseases etc. Clinical manifestations include fever, splenomegaly, lymphadenopathy, neurologic dysfunction, coagulopathy, features of sepsis etc. Laboratory investigation includes cytopenias, hypertriglyceridemia, hyperferritinemia, abnormal liver function, hemophagocytosis, and diminished NKcell activity. Treatment modalities include immunosuppressive, immunomodulatory agents, cytostatic drugs, T-cell antibodies, anticytokine agents and hematopoietic stem cell transplantation (HSCT). Besides those, aggressive supportive care combined with specific treatment of the precipitating factor can produce better outcome. With treatment more than 50% of children who undergo transplant survive, but adults have quite poor outcomes even with aggressive management. Faridpur Med. Coll. J. 2020;15(2): 98-102

Download Full-text

Neonatal Atrial Flutter: Case Report

Journal of Neonatology ◽

10.1177/09732179211065401 ◽

2021 ◽

pp. 097321792110654

Author(s):

Aashika Chandraprakasam ◽

Uma Muralidharan ◽

A. Kannan

Keyword(s):

Heart Failure ◽

Case Report ◽

Atrial Flutter ◽

Treatment Modalities ◽

Rare Entity ◽

Newborn Period ◽

Prompt Treatment ◽

Long Term Prognosis ◽

Prompt Diagnosis

Neonatal atrial flutter is a rare entity seen in the newborn period. With prompt treatment, they mostly revert to normal rhythm, with good long-term prognosis. But prolonged untreated atrial flutter can result in heart failure. This necessitates prompt diagnosis and treatment of the condition. However, all available treatment modalities are not effective in all patients. Here, we report 2 newborns with atrial flutter who did not respond initially to medical management, but eventually responded to cardioversion, with good outcome.

Download Full-text

Aanpak en behandelingsopties voor congenitale melanocytaire naevi

Tijdschrift voor Geneeskunde ◽

10.47671/tvg.77.21.082 ◽

2021 ◽

Author(s):

A. VANNESTE ◽

M. GARMYN ◽

M.-A. MORREN

Keyword(s):

Treatment Options ◽

Neurological Complications ◽

Treatment Modalities ◽

Melanocytic Nevi ◽

The Central Nervous System ◽

Magnetic Resonance Imaging Mri ◽

Long Term Prognosis ◽

Congenital Melanocytic Nevi

Management and treatment options in congenital melanocytic nevi Congenital melanocytic nevi (CMN) are benign collections of nevus cells in the skin. They are present at birth or arise during the first weeks of life. Depending on the size, they appear in 1 in 100 to 500.000 live births. CMN are associated with a variety of benign conditions such as benign proliferations, certain facial characteristics or subtle endocrine dysfunctions as well as malign developments such as melanoma and neurological complications. The risk for these complications strongly depends on the clinical phenotype. Magnetic resonance imaging (MRI) has a strong value in estimating the risk of these complications. A normal MRI of the central nervous system results in a lower risk of developing melanoma and neurological complications because of the thorough follow-up and early capture. Although there are various treatment modalities, a shift to more conservative treatment is seen. Little is known about the long term prognosis after treatment of CMN. This article tries to give a recommendation for treatment and follow-up of CMN based on the current literature.

Download Full-text