Pellagra in a child–A rare entity

This case has been presented as pellagra, which is very rare in children. Pellagra is due dietary deficiency of niacin. Usually seen in alcoholics, malabsorption syndromes occur very rarely in children. A 11-y-old girl presented with well-defined, hyperpigmented, hyperkeratotic, symmetrical, thick scaly plaques surrounded by erythema on the dorsum of the hands, arms, feet, legs up to knees, and along the sides of the neck. The child was given 100 mg of Nicotinamide. Skin lesions resolved rapidly with the treatment and the child improved.     

Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics

Purpose

Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.

Methods

Seventy ST cases on clopidogrel identified from the PLATO trial (n =?58) and Mayo Clinic biorepository (n =?12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.

Results

Poor metabolizers (n =?4) and rare CYP2C19*8, CYP2C19*15, and CYP2C19*11 alleles were identified only in ST cases. CYP2C19*17 heterozygote carriers were observed more frequently in cases (n =?29) than controls (n =?18). Functional studies of CYP2C19 exonic variants (n =?11) revealed 3 cases and only 1 control carrying a deleterious variant as determined by in vitro protein expression studies. Greater intronic variation unique to ST cases (n =?169) compared with controls (n =?84) was observed with predictions revealing 13 allele candidates that may lead to a potential disruption of splicing and a loss-of-function effect of CYP2C19 in ST cases.

Conclusion

NGS detected CYP2C19 poor metabolizers and paradoxically greater number of so-called rapid metabolizers in ST cases. Rare deleterious exonic variation occurs in 4%, and potentially disruptive intronic alleles occur in 16% of ST cases. Additional studies are required to evaluate the role of these variants in platelet aggregation and clopidogrel metabolism.

     

Traumatic tricuspid papillary muscle and chordae rupture: emerging role of three-dimensional echocardiography

We describe a patient with blunt traumatic chest injury in whom three-dimensional transthoracic echocardiography (3DTTE) confirmed the findings of a flail anterior tricuspid valve leaflet and ruptured anterior papillary muscle seen on two-dimensional transthoracic echocardiography, and in addition identified multiple chordae tendinae rupture of the posterior leaflet. Open heart surgery confirmed the findings. The emerging role of 3DTTE in defining the true extent of traumatic tricuspid valvular injury is highlighted .     

Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia

The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76.8%), grade 1 in 16 patients (19.5%), and grade 0 in 3 patients (3.7%). Grade 2 fibrosis was associated with reduced hemoglobin levels (median 9.75 vs 11.0 g/dL in grade 0/1; p?=?0.04) and increased percentages of ringed sideroblasts (7.5 vs 0%; p?=?0.008). In multivariable analysis, grade 2 fibrosis was an independent predictor of poor overall survival (OS; 95% CI 1.32–6.35; HR 2.90; p?=?0.008), but not event-free survival (EFS; 95% CI 0.62–2.67; HR 1.28; p?=?0.50). Absolute neutrophil count (ANC) was found to impact OS (95% CI 1.01–1.09; HR 1.05; p?=?0.009), while both ANC (95% CI 1.00–1.07; HR 1.04; p?=?0.04) and peripheral blood blast percentage (95% CI 1.02–1.32; HR 1.16; p?=?0.02) impacted EFS. These results implicate fibrosis grade is an important indicator of prognosis, with high-grade fibrosis predicting inferior survival. Given the prevalence of marrow fibrosis in CMML, fibrosis grading should be incorporated into prognostic assessment and therapeutic decision-making.     

Syncope in a middle aged male due to acute rheumatic fever

Rheumatic fever is a multi system disease which occurs following infection with group A beta hemolytic streptococcus. It is commonest in the age group of 5-15 years but can occur in adults also. First degree atrioventricular block is a common manifestation of acute rheumatic fever and is included in the Jones criteria but Wenckebacks phenomena and complete heart block are relatively rare manifestations of rheumatic fever. Syncope occurring in acute rheumatic fever is also infrequently reported. We report the case of a 38-year-old male with rheumatic carditis who had advanced atrioventricular block which resulted in syncope and required a temporary pacemaker insertion.     

Embracing Technology for Capacity Building in Mental Health: New Path,Newer Challenges

Psychiatric Quarterly - Technology driven capacity building initiatives are the way to break the barrier of shortage of mental health human resources in India. This new path, while is a welcome...