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Abstract: Objective: We have previously reported that surgical removal of the nasopharyngeal adenoid in young children resulted in increased risk of nasopharyngeal colonization by pneumococci. We now investigated whether adenoidectomy influences the development of serum IgG antibodies to pneumococcal choline-binding protein A (CbpA) and pneumococcal surface protein A (PspA). Methods: Altogether 217 children aged 12–48months who had recurrent or persistent otitis media were randomized to undergo or not to undergo adenoidectomy. All the children underwent insertion of tympanostomy tubes. 166 children were followed-up for 3years. The main outcome measures were concentrations of serum IgG antibodies to CbpA and PspA three years after randomization. Nasopharyngeal colonization by pneumococci was assessed 1, 2, and 3years after randomization. Results: Adenoidectomy decreased concentrations of CbpA antibodies by ca. 25% independently of the observed increase in pneumococcal carriage (OR of log10 transformed concentrations 0.74, 95% CI 0.58–0.94, P =0.016). Concentrations of PspA antibodies were lower and they seemed not to be influenced by adenoidectomy. Conclusions: Adenoidectomy in young children causes a small but detectable impairment in the development of serum IgG antibodies to pneumococcal CbpA. The adenoid seems to have a role in augmenting systemic immunity against pneumococci. [Copyright &y& Elsevier]

Background & Aims: Treatment of recurrent Clostridium difficile infection (CDI) with antibiotics leads to recurrences in up to 50% of patients. We investigated the efficacy of fecal transplantation in treatment of recurrent CDI. Methods: We reviewed records from 70 patients with recurrent CDI who had undergone fecal transplantation. Fecal transplantation was performed at colonoscopy by infusing fresh donor feces into cecum. Before transplantation, the patients had whole-bowel lavage with polyethylene glycol solution. Clinical failure was defined as persistent or recurrent symptoms and signs, and a need for new therapy. Results: During the first 12 weeks after fecal transplantation, symptoms resolved in all patients who did not have strain 027 C difficile infections. Of 36 patients with 027 C difficile infection, 32 (89%) had a favorable response; all 4 nonresponders had a pre-existing serious condition, caused by a long-lasting diarrheal disease or comorbidity and subsequently died of colitis. During the first year after transplantation, 4 patients with an initial favorable response had a relapse after receiving antibiotics for unrelated causes; 2 were treated successfully with another fecal transplantation and 2 with antibiotics for CDI. Ten patients died of unrelated illnesses within 1 year after transplantation. No immediate complications of fecal transplantation were observed. Conclusions: Fecal transplantation through colonoscopy seems to be an effective treatment for recurrent CDI and also for recurrent CDI caused by the virulent C difficile 027 strain. [ABSTRACT FROM AUTHOR]

Abstract: Background: Merkel cell polyomavirus (MCPyV) was identified newly (2008) and is believed to be an etiologic factor of Merkel cell carcinoma (MCC). Recent molecular and serological data suggest that MCPyV infection is common in the general population. Objectives: The aim of this study was to investigate the age of primary exposure to MCPyV. Study design: A MCPyV-IgG EIA was developed using the MCPyV major capsid protein VP1 expressed and self-assembled into virus-like particles (VLPs) in insect cells. The assay was used to detect serum IgG antibodies in two groups of children. Group 1 comprised paired and 5–8 year follow-up sera from 217 children (3–13 years) with acute lower respiratory tract infection. Group 2 comprised sera from 158 children (1–4 years) with otitis media; 86 children underwent adenoidectomy and 72 did not, whereafter follow-up sera were obtained 3 years later. Result: The prevalence of MCPyV-IgG was 9% at 1–4 years, and increased to 35% at 4–13 years among subjects from Group 1, with a 33% seroconversion rate during 5–8 years. Among Group 2, the seroconversion rate was 16% during 3 years. The IgG prevalence at 4–7 years as well as the IgG levels showed an apparent gender difference, with male preponderance prevailing among the children without adenoidectomy. Conclusion: MCPyV primary infections occur ubiquitously in childhood, and the first exposure takes place at young age. The serology showed no evidence for a causative role of MCPyV in lower respiratory tract infection manifesting as acute wheezing, but was compatible with the notion of MCPyV persistence in tonsils. [ABSTRACT FROM AUTHOR]

Summary: Cancer invasion induces extracellular matrix remodeling and collagen degradation. The aim of this study was to assess whether serum levels of type I and III collagen degradation products were associated with patient survival in head and neck squamous cell carcinoma (HNSCC). A novel enzyme immunoassay was developed for measuring type III collagen N-terminal telopeptide (IIINTP) in human serum samples. In addition, type I collagen C-terminal telopeptide (ICTP), matrix metalloprotease-8 (MMP-8) and tissue inhibitor of metalloproteases-1 (TIMP-1) were assessed in 205 blood samples from HNSCC patients. High levels of serum ICTP and IIINTP and plasma TIMP-1 were associated with poor survival. The concentration of ICTP was associated with levels of IIINTP and TIMP-1. The plasma concentration of MMP-8 was associated with tumor stage, but not with survival or levels of ICTP, IIINTP or TIMP-1 suggesting that other collagenases/proteases are responsible for the cleavage of type I and type III collagens. The rate of type I and type III collagen degradation is associated with patient survival and can be used as a prognostic marker in HNSCC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Otitis media is a multifactorial disease where genetic background may have an important role. For genome-wide association studies, it is important to understand the degree of heritability. The objective of this study was to estimate the heritability of recurrent acute otitis media and chronic otitis media with effusion. Methods: Children operated because of recurrent or chronic otitis media at the Helsinki University Central Hospital, Finland, as well as their families were recruited during 2008–2009. A cohort of 2436 subjects was enrolled consisting of 1279 children and their parents. The study subjects answered a questionnaire concerning their otitis media history and treatment, as well as tobacco exposure, allergy and asthma history. Heritability estimates were calculated for recurrent acute, chronic and any episodes of otitis media using software especially designed for estimating heritability in family cohorts. Results: Altogether 901 subjects suffered from recurrent otitis media and 559 from chronic otitis media with effusion. The heritability estimates in our cohort were 38.5% for recurrent (P =7.3×10−9), 22.1% for chronic (P =4.6×10−3) and 47.8% for any otitis media (P =1.5×10−11). Conclusions: Our results demonstrate a moderately strong and statistically significant genetic component for both recurrent acute otitis media and chronic otitis media with effusion. These results highlight the importance of unraveling the genetic factors for otitis media that are still poorly known. [Copyright &y& Elsevier]

Summary: Expression of matrix metalloproteinase-8 (MMP-8) in tongue cancer cells has been associated with an improved prognosis. MMP-8 is inhibited by tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and elevated levels of TIMP-1 in blood have been associated with poor prognosis in many cancers. We wished to evaluate the usefulness of peripheral blood MMP-8 and TIMP-1 levels as well as the genotypes of MMP8 and TIMP1 in predicting prognosis in head and neck squamous cell carcinoma (HNSCC). Plasma concentrations of MMP-8 and TIMP-1 were analyzed in 136 HNSCC patients. MMP8 and TIMP1 genotypes were determined by analysis of single nucleotide polymorphisms (SNP) in peripheral blood DNA. The mean follow-up time was 3.3years. We found that plasma MMP-8 level did not predict survival but that TIMP-1 level was associated with survival. The adjusted hazard ratio of death scored as a continuous variable on the log10 scale was 23.2 (95% CI 1.88–286, P =0.01) and that of MMP-8 1.24 (95% CI 0.54–2.84, P =0.61). Immunohistochemical staining showed that TIMP-1 was expressed in vascular endothelium of tumor. TIMP-1 levels were associated with TIMP1 genotype in women but not in men. MMP8 genotype did not correlate with survival or MMP-8 level. Plasma TIMP-1 levels predict survival in HNSCC. TIMP-1 expression is genetically controlled in women. As TIMP-1 inhibits the activity of MMP-8 and it also functions as a growth factor, it may directly influence HNSCC progression. [Copyright &y& Elsevier]

Summary: Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by severe mucosal reactions. We have recently shown that the single nucleotide polymorphism (SNP) rs1982073 of the TGFβ1 gene (TGFB1) is associated with the survival of HNSCC patients who have undergone CRT. In order to evaluate possible mechanisms mediating this, we investigated if the TGFB1 polymorphism was associated with the severity of mucositis induced by CRT. Peripheral blood DNA of 34 HNSCC patients who had undergone CRT was genotyped for the SNP rs1982073 of the TGFB1. Mucositis was graded according to acute toxicity criteria of radiation therapy oncology group (RTOG). The mean follow-up time was 48months (range, 4–115months). We did not find a significant association between the TGFB1 polymorphism and the degree of acute mucositis (OD=2.65; 95% CI 0.50–13.89; p =0.25). The degree of acute mucositis was not connected to disease-free survival (p =0.35). However, the TGFB1 polymorphism was associated with survival irrespective of the degree of mucositis (HR=3.23; 95% CI 1.19–8.77; p =0.02). [Copyright &y& Elsevier]

Summary: Objective: Exposure to environmental tobacco smoke has been reported to be a risk factor for childhood otitis media. The effect of parental smoking on the risk of otitis media after the insertion of tympanostomy tubes is unknown. We evaluated the effect of parental smoking on the risk of recurrent otitis media in children who had received tympanostomy tubes. Methods: We enrolled 217 children aged 1–4 years who underwent insertion of tympanostomy tubes because of middle ear disease. The children were followed-up for 12 months. Otitis media episodes were recorded in patient diaries by primary care physicians. Parental smoking habits were assessed by a questionnaire at the start of the trial and after the 12 month follow-up had ended. The main outcome measure was risk of recurrent otitis media as defined by four or more otitis media episodes after tympanostomy. Altogether 198 children completed the follow-up. Results: Maternal smoking was associated with a highly increased risk of recurrent acute otitis media (OR 4.15, 95% CI 1.45–11.9) after the insertion of tympanostomy tubes. Conclusion: Exposure to passive smoking is associated with four-fold risk of recurrent otitis media after tympanostomy. This finding should be used to encourage parents to stop smoking even after the insertion of tympanostomy tubes to their children. [Copyright &y& Elsevier]