Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse

Background Less than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations have suggested significant genetic divergence of the relapsed disease. Methods We undertook large-scale integrated characterization of the molecular features of rMB—molecular subgroup, novel subtypes, copy number variation (CNV), and driver gene mutation. 119 rMBs were assessed in comparison with their paired diagnostic samples (n = 107), alongside an independent reference cohort sampled at diagnosis (n = 282). rMB events were investigated for association with outcome post-relapse in clinically annotated patients (n = 54). Results Significant genetic evolution occurred over disease-course; 40% of putative rMB drivers emerged at relapse and differed significantly between molecular subgroups. Non-infant MBSHH displayed significantly more chromosomal CNVs at relapse (TP53 mutation-associated). Relapsed MBGroup4 demonstrated the greatest genetic divergence, enriched for targetable (eg, CDK amplifications) and novel (eg, USH2A mutations) events. Importantly, many hallmark features of MB were stable over time; novel subtypes (>90% of tumors) and established genetic drivers (eg, SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (eg, DNA damage signaling) and specific events (eg, 3p loss) predicted survival post-relapse. Conclusions rMB is characterised by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course

Current clinical profile of respiratory diseases in geriatric population

Study of current clinical profile of respiratory diseases in geriatric population. We have taken 1234 patients for study in which males were773 females were 461. 394 patients required inpatient respiratory critical care with community acquired pneumonia, bronchogenic carcinoma, acute respiratory tract infections, acute exacerbation of COPD, bronchial asthma exacerbations and other pleural diseases. 890 patients belong to the age group 65-74yrs and 344 in 75+ yrs age group .studied demographic patient age, sex distribution above the age of 65yrs with more prevalence in males. Respiratory diagnosis in geriatric population upper respiratory tract infections percentage diagnosis is higher. Respiratory diagnosis of inpatient respiratory diseases highest is the acted exacerbation of the COPD. In pneumonia community acquired pneumonia high prevalence in age and sex distribution and highest isolated micro organisms is staphylococcus. For pulmonary TB males are higher with isolated new sputum positive cases

To establish the role of HRCT in the early diagnosis of pulmonary disease in symptomatic HIV sero-positive patients with normal chest radiograph

In our study of 352 HIV[2] seropositive patients with pulmonary symptoms , 34 patients had normal chest radiograph which is equivalent to 9.66%this value correlates with the study conducted by john segreti et al , who demonstrated the chest radiograph were normal in 10% of his HIV patients with pulmonary symptoms . Among these 34 patients three patients did not turn up for further investigations. Hence only 31 patients were included in this study. In the present study 90.31% of patients belonged to the age group ranging from 20 – 40 years with a mean age of 30.3 years. As this is economically the most productive age group , early diagnosis and treatment of pulmonary disease decreased the morbidity and mortality and economic burden on the society . palmieri F , girandi E et al , in their retrospective study on 146 HIV[2] seropositive patients observed a decrease in survuival among patients with pulmonary TB[1] negative sputum smear and normal chest X- ray at presentation . This was primarily attributed to the delay in the diagnosis of TB and initiation of atituberculosis treatment which results in faster progression of HIV infection . This highlights the importance of early diagnosis and treatment in symptomatic HIV seropositive patients with normal chest x-ray findings in India, where TB contributes the major share for the morbidity and mortality of HIV infection . In this study , lesions in the right and left lung were seen in 8 cases each and in both lungs in 16.12% cases . In the right lung , lesions were seen in 12.9% cases in the upper lobe , 6.45% in middle lobe and 6.45% cases in the lower lobe In the left lung lesions were seen 16.12% cases in the upper lobe , 6.45% cases in the lingual , in 3.22% cases in lower lobe . High resolution CT helps in localizing in the lung where further diagnostic investigations like bronchoscopy , broncho alveolar lavage(BAL)[4] and fine needle aspiration cytology (fnac) can be done where ever necessary. This observation was supported by Kirshenbaum KJ, burke R et al in their study conducted in January 1998. In the present study the following were the CT findings consolidation in 4 cases (12.9%), fibrosis and bronchiectasis in 3 cases(9.67%) and blebs,bullae,ground glass appearance and hilar adenopathy in 1 case (3.22%) each. These findings can help us to suspect it diagnosis and guide us to select necessary specific, invasive and laborious investigations like bronchoscopy ,BAL,FNAC,sputum culture for TB bacilli, staining for pneumocystis carinii etc. to come a specific diagnosis.gruden JF , huang L et al in their study concluded that empirical therapy or immediate bronchoscopy can be avoided in many patients of PCP [3]on the basis of the HRCT findings