Association Between Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection in Early Life and Recurrent Wheeze and Asthma in Later Childhood.

BACKGROUND: Recurrent wheeze and asthma in childhood are commons causes of chronic respiratory morbidity globally. We aimed to explore the association between respiratory syncytial virus (RSV) infection in early life and subsequent respiratory sequelae up to age 12 years. METHODS: We estimated the strength of association by 3 control groups and 3 follow-up age groups, with data from studies published between January 1995 and May 2018. We also estimated associations by diagnostic criteria, age at infection, and high-risk population. RESULTS: Overall, we included 41 studies. A statistically significant association was observed between early life RSV infection and subsequent childhood recurrent wheeze, in comparison to those who were healthy or those without respiratory symptoms: OR 3.05 (95% confidence interval [CI], 2.50-3.71) for 0 to <36 months follow-up age; OR 2.60 (95% CI, 1.67-4.04) for 36-72 months; and OR 2.14 (95% CI, 1.33-3.45) for 73-144 months. For the subsequent development of asthma, a statistically significant association was observed only in relation to those aged 73-144 months at follow-up: OR 2.95 (95% CI, 1.96-4.46). CONCLUSIONS: Further studies using standardized definitions and from diverse settings are needed to elucidate the role of confounders and provide more robust estimates.

Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma.

Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well-established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q-PIK3CA, TP63; 11q13.3-CCND1, ANO1) in tumor DNA recovered from HPSCC (n = 48) and OPSCC (n = 52) patients. Associations between copy number gain, patient demographics, HPV/p16INK4a status and pathological stage were examined. HPV/p16 prevalence in HPSCC and OPSCC groups was 2.1% and 46.0%, respectively. HPSCCs had frequent gains of CCND1 (56.3%) and ANO1 (56.3%) but few gains of PIK3CA (6.3%). By contrast, OPSCCs had significantly fewer CCND1 (23.1%) and ANO1 (17.3%) gains, and significantly more PIK3CA (26.9%) gains. A mutually exclusive relationship between HPV/p16 and 11q13.3 gains was observed in OPSCCs, while PIK3CA and TP63 gains were similar across HPV-associated and smoking/alcohol-associated patients. ANO1 gain was significantly linked to tumor pathology in HPSCC, associating with nodal metastasis and smaller and less invasive tumors at presentation (P = 0.010). Our results provide a convincing link between a specific molecular change and disease phenotype that appears unique to our HPSCC population, supporting a model of 11q13.3 in promoting metastatic disease progression in HNSCC, and suggest a role for ANO1 as a molecular marker of metastatic disease. © 2016 Wiley Periodicals, Inc.

Drug resistant TB - latest developments in epidemiology, diagnostics and management.

AIM: The aim of this review is to inform the reader on the latest developments in epidemiology, diagnostics and management. EPIDEMIOLOGY: Drug-resistant Tuberculosis (DR-TB) continues to be a current global health threat, and is defined by higher morbidity and mortality, sequelae, higher cost and complexity. The WHO classifies drug-resistant TB into 5 categories: isoniazid-resistant TB, rifampicin resistant (RR)-TB and MDR-TB, (TB resistant to isoniazid and rifampicin), pre-extensively drug-resistant TB (pre-XDR-TB) which is MDR-TB with resistance to a fluoroquinolone and finally XDR-TB that is TB resistant to rifampicin, plus any fluoroquinolone, plus at least one further priority A drug (bedaquiline or linezolid). Of 500,000 estimated new cases of RR-TB in 2020, only 157 903 cases are notified. Only about a third of cases are detected and treated annually. DIAGNOSTICS: Recently newer rapid diagnostic methods like the GeneXpert, whole genome sequencing and Myc-TB offer solutions for rapid detection of resistance. TREATMENT: The availability of new TB drugs and shorter treatment regimens have been recommended for the management of DR-TB. CONCLUSION: Despite advances in diagnostics and treatments we still have to find and treat two thirds of the drug resistant cases that go undetected and therefore go untreated each year. Control of TB and elimination will only occur if cases are detected, diagnosed and treated promptly.