Profiling system-wide variations and similarities between Rheumatic Heart Disease and Acute Rheumatic Fever-A pilot analysis.

Rheumatic heart disease (RHD) continues to affect developing countries with low income due to the lack of resources and effective diagnostic techniques. Understanding the genetic basis common to both the diseases and that of progression from its prequel disease state, Acute Rheumatic Fever (ARF), would aid in developing predictive biomarkers and improving patient care. To gain system-wide molecular insights into possible causes for progression, in this pilot study, we collected blood transcriptomes from ARF (5) and RHD (5) patients. Using an integrated transcriptome and network analysis approach, we identified a subnetwork comprising the most significantly differentially expressed genes and most perturbed pathways in RHD compared to ARF. For example, the chemokine signaling pathway was seen to be upregulated, while tryptophan metabolism was found to be downregulated in RHD. The subnetworks of variation between the two conditions provide unbiased molecular-level insights into the host processes that may be linked with the progression of ARF to RHD, which has the potential to inform future diagnostics and therapeutic strategies. We also found a significantly raised neutrophil/lymphocyte ratio in both ARF and RHD cohorts. Activated neutrophils and inhibited Natural Killer cell gene signatures reflected the drivers of the inflammatory process typical to both disease conditions.

Thiamine-responsive acute severe pulmonary hypertension in exclusively breastfeeding infants: a prospective observational study.

OBJECTIVES: Severe pulmonary hypertension (PH) causing right heart failure can occur due to thiamine deficiency in exclusively breastfeeding infants. This study describes the clinical profile and management of thiamine-responsive acute pulmonary hypertension. METHODS: A prospective observational study of infants presenting with severe PH without any other significant heart or lung disease. History of symptoms, clinical examination, echocardiography and basic investigations were performed. Dietary patterns of mothers were recorded. Thiamine was administered and serial echocardiography was performed. RESULTS: A total of 250 infants had severe PH and 231 infants responded to thiamine. The mean age was 3.2±1.2 months. Fast breathing, poor feeding, vomiting and aphonia were the main symptoms. Tachypnoea, tachycardia and hepatomegaly were found on examination. Echocardiogram revealed grossly dilated right heart with severe PH. Intravenous thiamine was administered to all the babies based on clinical suspicion. Clinical improvement with complete resolution of PH was noticed within 24-48 hours. Babies were followed up to a maximum of 60 months with no recurrence of PH. All the mothers consumed polished rice and followed postpartum food restriction. CONCLUSION: Thiamine deficiency is still prevalent in selected parts of India. It can cause life-threatening PH in exclusively breastfeeding infants of mothers who are on a restricted diet predominantly consisting of polished rice. It can contribute to infant mortality. Thiamine administration based on clinical suspicion leads to remarkable recovery. High degree of awareness and thiamine supplementation in relevant geographical areas is required to tackle this fatal disease.