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Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC. Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations. Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other. Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997–2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry. Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T- and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found. [ABSTRACT FROM AUTHOR]

Conclusions: The incidence of oropharyngeal squamous cell cancer (OPSCC) in Finland has increased during the past decades. A similar change has been seen in the relative frequency of p16-positive head and neck squamous cell carcinoma (HNSCC). As p16 is a surrogate marker for human papilloma virus (HPV) infection, and as most p16-positive HNSCCs are OPSCC, HPV infection may have had a role in the observed increased incidence of OPSCC. Objectives: Numerous studies have shown that HPV is an independent risk factor for OPSCC. We aimed to use p16 as a surrogate marker of HPV infection to study its role as a possible risk factor in OPSCC. Furthermore, the change in the incidence of OPSCC in Finland was studied. Methods: HPV status was determined by p16 immunohistochemistry of 135 HNSCC tumour specimens retrieved from patients treated at the Helsinki University Central Hospital. Incidence data on OPSCC were obtained from the Finnish Cancer Registry. Results: The incidence of OPSCC in Finland increased from 0.66/100 000 person-years during 1989--1993 to 1.36 during 2004--2008. During the same period a significant increase in the relative frequency of p16 positive HNSCC tumours from 22% during 1990--1999 to 41% during 2000--2007 could be seen at our institution. In all, 85% of the p16-positive specimens were OPSCC. [ABSTRACT FROM AUTHOR]

Background: Fusobacterium species are anaerobic bacteria that relatively rarely cause sepsis with a variable clinical presentation. Methods: We reviewed the records of 52 consecutive patients who had Fusobacterium bacteraemia over a 10-y period. Results: The clinical pictures could be classified into 4 groups: (1) patients who had Lemierre's syndrome with Fusobacterium necrophorum sepsis and internal jugular vein thrombosis, n == 5 (10%); (2) previously healthy patients who had F. necrophorum sepsis without any signs of macroscopic vascular thrombosis (but 5 of them had abscesses), n == 14 (27%); (3) women who had puerperal infections, n == 6 (12%); and (4) patients who were on average older than the patients in the previous groups, who had cardiovascular, pulmonary, neoplastic, or other underlying diseases, n == 27 (52%). Of these latter 27 patients, 23 had nosocomial Fusobacterium nucleatum bacteraemia presenting as a febrile illness associated with chemotherapy or instrumentation. Conclusions: Patients with chronic underlying diseases are more likely to be infected with F. nucleatum than F. necrophorum. F. nucleatum bacteraemia may present as a febrile illness without severe symptoms. F. necrophorum caused sepsis mainly in previously healthy individuals. These infections may be accompanied with a jugular vein thrombosis characteristic of Lemierre's syndrome and septic shock. However, F. necrophorum infections present more frequently without any apparent venous thrombosis and may be accompanied by abscesses. [ABSTRACT FROM AUTHOR]

Conclusion. The finding of several new unique mutations suggests that the genes causing hereditary hemorrhagic telangiectasia (HHT), i.e. endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1), have a relatively high mutation rate. As no single founder mutation was found, analysis of the whole coding sequences of ENG and ACVRL1 genes remains the first choice in genetic testing of new index patients with HHT. Objectives. Our aim was to characterize specific mutations causing HHT in our hospital in Helsinki serving a population of 1 million inhabitants. Patients and methods. HHT patients were searched from our hospital discharge records and their diagnoses were verified by review of patient records and interviews. Eight index patients who fulfilled HHT phenotypic criteria were tested. ENG and ACVRL1 mutations were identified by DNA sequencing of ENG and ACVRL1 coding regions. Results: Of the eight index patients, four had a mutation in the ENG gene, three in the ACVRL1 gene, and one had no mutations. All the mutations were different and all the four ENG mutations and one of the ACVRL1 mutations were new and had not been described previously in other populations. All the affected first-degree relatives had the same mutation as the index case. [ABSTRACT FROM AUTHOR]

Conclusion: Tuberculosis is a rare disease that can mimic a neck malignancy. It should be taken into consideration when evaluating a patient with a neck mass, especially when the patient has come from an area of high endemic incidence. Another risk group comprises older people with dormant tuberculosis. Objectives: We wanted to find out the incidence of head and neck tuberculosis in Finland and to define the factors that should make one suspect it. Patients and methods: This was a retrospective analysis of patients who were diagnosed with tuberculosis in the Department of Otolaryngology, Helsinki University Central Hospital (population base c.a. 1 000 000) during 1996-2005. All the patients with culture- or PCR-positive tuberculosis were included. Results: During 1996-2005, 63 patients were diagnosed with head and neck tuberculosis, the average incidence being 0.6/100 000 per year. The age of the patients varied between 3 and 94 years (mean 47 years). The mean age of patients who were of Finnish extraction (37 patients) was 62 years and that of immigrants (26 patients) was 27 years. Forty-four (70%) patients were female and 19 (30%) male. The majority of patients presented with a neck mass without symptoms of general infection such as fever or fatigue. [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]

Aim: To determine if there is an association between ABO variants or blood types and otitis media. Methods: DNA samples from 214 probands from Finnish families with recurrent acute (RAOM) and/or chronic otitis media with effusion (COME) were submitted for exome sequencing. Fisher exact tests were performed when (a) comparing frequencies of ABO genotypes in the Finnish probands with otitis media vs. counts in gnomAD Finnish, and (b) within the Finnish family cohort, comparing occurrence of RAOM vs. COME according to ABO genotype/haplotype and predicted blood type. Results: Female sex is protective against having both RAOM and COME. The wildtype genotype for the ABO c.260insG (p.Val87_Thr88fs*) variant resulting in blood type O was protective against RAOM. On the other hand, type A was associated with increased risk for COME. These findings remained significant after adjustment for age and sex. Conclusions: Within the Finnish family cohort, the wildtype genotype for the ABO c.260insG (p.Val87_Thr88fs*) variant and type O are protective against RAOM while type A increases risk for COME. This suggests that the association between the ABO locus and otitis media is specific to blood type, otitis media type and cohort.

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media., (© 2019 Wiley Periodicals, Inc.)

Background: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC., Materials and Methods: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS)., Results: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels., Conclusion: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.

Background:  Clostridium difficile causes diarrhea that ranges from a benign, self-limiting antibiotic use-associated disease to a life-threatening pseudomembranous colitis. Clostridium difficile has rarely been isolated in extraintestinal infections. Our objective was to characterize clinical features and risk factors of these infections. METHODS Extraintestinal C. difficile infections (CDIs) were searched for in an electronic database of all C. difficile-positive isolates found during a 10-year period. The medical records were reviewed retrospectively. Disease severity and comorbidities of the patients were evaluated using Horn disease severity and Charlson comorbidity indexes., Results:  Extraintestinal CDI was found in 31 patients who comprised 0.17% of all CDIs. Two patients had bacteremic infections, 4 had abdominal infections without any prior surgery, 7 had abdominal infections after surgery, 4 had perianal abscesses, 13 had wound infections, and 1 had C. difficile in a urinary catheter. In most cases (85%), C. difficile was isolated together with other microbes. Most (81%) patients developed the infection when hospitalized and many had severe comorbidities. Sixteen (52%) had diarrhea. The 1-year mortality rate was 36% and it correlated with the severity of underlying diseases., Conclusions:  Extraintestinal CDIs occur mainly in hospitalized patients with significant comorbidities. Extraintestinal CDIs in the abdominal area may result from either intestinal perforation after infection or after intestinal surgery. Wound infections may result from colonization by feces. Clostridium difficile may reach distant sites via bacteremia. Mortality in extraintestinal CDIs is associated with the severity of underlying diseases.

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., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Trichodysplasia spinulosa (TS)-associated polyomavirus (TSV) was recently (in 2010) discovered in TS lesions. To investigate the seroprevalence and primary exposure time of this virus, we set up a virus protein (VP1) viruslike particle (VLP)-based immunoglobulin G enzyme immunoassay. The seroprevalence of TSV was 5%, among children aged 1-4 years, rising to 48% at 6-10 years, and 70% among 149 adults. The TSV antibodies did not cross-react with corresponding Merkel cell polyomavirus VLPs, and their reactivity appeared conformational. TSV circulates widely in the human population and primary exposure is extensive in childhood, beginning at age 1-2 years.

The objective of the study was to evaluate the risk of asthma in children who had undergone an adenoidectomy, an operation frequently performed on children with glue ear or recurrent otitis media. Two surveys were carried out, a nation-wide questionnaire returned by 483 individuals (survey A) and a survey of hospital discharge records involving 1616 children who had undergone an adenoidectomy and 161 control children who had undergone probing of the nasolacrimal duct due to congenital obstruction (survey B). The questionnaire (survey A) showed that an adenoidectomy before the age of 4 years was associated with asthma (OR 3.19, 95% CI 1.25; 8.13) and with allergy to animal dust (OR 2.50, 95% CI 1.27; 4.95). In survey B, asthma diagnosis was retrieved from the national asthma register. It showed also that adenoidectomy at an early age was associated with an increased risk of asthma (OR 6.74, 95% CI 2.99; 15.2). There was an association between asthma and adenoidectomy, even before adenoidectomy had actually been performed. The risk of asthma was highest among children who had had adenoidectomy because of recurrent otitis media. The observed association between an adenoidectomy and asthma may be explained by an underlying factor predisposing to both recurrent otitis media and asthma.