Helsinki University Central Hospital Research Articles

Does Time of Day Or Physician Experience Affect Outcome of Acute Ischemic Stroke Patients Treated with Thrombolysis? a Study from Finland

Maintaining a steady thrombolysis service for treatment of acute ischemic stroke 24 h/7 days is challenging. Diurnal and seasonal variability of stroke onset affects the clinical outcome of these patients. We state that a 24 h/7 days availability of stroke-trained physicians ameliorates weekend effects and other seasonal, weekday, or non-office-hour-related influences on outcome of ischemic stroke patients treated with intravenous thrombolysis. All consecutive ischemic stroke patients treated with thrombolysis at the Helsinki University Central Hospital were prospectively registered (n = 1581). Patients with basilar artery occlusion (n = 154) were excluded. Door-to-needle time, three-month clinical outcome as measured by the modified Rankin Scale dichotomized at 0 to 2 vs. 3 to 6, and symptomatic intracerebral hemorrhage were analyzed with logistic regression models adjusting for baseline variables. The treating physician was defined as experienced after 18 decisions made to give thrombolysis treatment. Door-to-needle time or clinical outcome did not differ with regard to time of day or season of presentation. Higher rates of symptomatic intracerebral hemorrhage occurred in spring (odds ratio 2·06, 95% confidence interval 1·03-4·11) and fall (odds ratio 2·08, 95% confidence interval 1·03-4·18). Physician experience reduced the door-to-needle time (odds ratio 0·40, 95% confidence interval 0·32-0·50) but was not associated with patient outcome (modified Rankin scale 3 to 6, odds ratio 1·22, 95% confidence interval 0·95-1·59) or symptomatic intracerebral hemorrhage (odds ratio 0·80, 95% confidence interval 0·51-1·27) rates. Thrombolytic therapy can be delivered at a steady service level at all times. With proper training, less-experienced physicians can provide high quality thrombolysis, but experience translates into faster treatment.

Prevention of relapses of nasal polyposis with intranasal triamcinolone acetonide after polyp surgery: A prospective double‐blind, placebo‐controlled, randomised study with a 9‐month follow‐up

To determine whether intranasal triamcinolone acetonide prevents the regrowth of nasal polyps after polyp surgery. Randomised, double-blind, placebo-controlled, prospective study. Helsinki University Central Hospital. Sixty patients with nasal polyps entered the study. Patients were included upon arrival for elective polyp operations determined according to our standard clinical criteria. The recurrence of nasal polyposis was followed up for 9 months after surgical treatment at 3-month intervals. Anterior rhinoscopy, nasal endoscopy, olfactory threshold measurement, active anterior rhinomanometry and acoustic rhinometry were performed at every follow-up visit. On the whole, there was a significant inter-group difference in the change in polyp size of acetylsalicylic acid (ASA)-tolerant patients during the follow-up. In patients with acetylsalicylic acid intolerance, there was no inter-group difference (P = 0.28). No significant differences were noted for nasal resistance, nasal cavity volume, sense of smell and nasal symptoms. Triamcinolone acetonide prevents regrowth of nasal polyps after polyp surgery in acetylsalicylic acid-tolerant patients, but not in acetylsalicylic acid-intolerant patients.

Management and outcome of salivary duct carcinoma in major salivary glands

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with poor prognosis. Its histomorphology is distinctly reminiscent of the ductal carcinoma of the breast. We reviewed the treatment and outcome of SDCs at a single tertiary care centre. Twenty-five cases of SDC of major salivary gland origin, diagnosed and treated at the Department of Otolaryngology, Head and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland, during a 14-year period from 1997 to 2011, were reviewed retrospectively. Survival outcome was analyzed for 18 patients with a minimum follow-up of 24 months. There were 16 male (64 %) and 9 female (36 %) patients with a median age of 61 years (range 36-82 years). The majority of the cases occurred in the parotid gland (n = 21, 84 %) followed by the submandibular gland (n = 4, 16 %). The primary treatment consisted of surgical resection in all cases and 17 (68 %) patients also underwent neck dissection. Most of the patients (n = 18, 72 %) were treated with postoperative radiotherapy. Seven patients (28 %) had a disease recurrence within a median follow-up time of 15 months (range 3-27 months). In the group (n = 18) with a minimum follow-up time of 24 months, the 2- and 5-year overall and disease-specific survival rates were 66, 41 % and 75, 55 %, respectively. These results confirm the aggressive nature of SDCs in major salivary glands. Diagnostics and management of these tumours need to be centralized in experienced surgical Head and Neck Oncology Centres, and new treatment strategies should be investigated.

Cerebral Edema in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

Cerebral edema (CED) deteriorates outcome of ischemic stroke patients, and there is no effective medical treatment. Limited data exist on cerebral edema after stroke thrombolysis. We aimed to analyze impact of cerebral edema on the outcome of thrombolysis-treated patients. Our cohort included 943 thrombolysis-treated ischemic stroke patients at the Helsinki University Central Hospital (1995-2008). Cerebral edema represented focal brain swelling up to 1/3 (CED-1) or greater than 1/3 (CED-2) of the hemisphere, or midline shift (CED-3). We studied baseline parameters associated with development of cerebral edema and association of cerebral edema with three-month outcome (modified Rankin Scale, mRS). On control imaging, CED-1 was present in 167 (17·7%), CED-2 in 40 (4·2%), and CED-3 in 53 (5·6%) patients. Compared with patients without edema (n = 683), patients with cerebral edema had higher baseline National Institutes of Health Stroke Scale scores, more often hyperdense cerebral artery sign or early infarct signs on admission computerized tomography, and received thrombolysis later. Cerebral edema was independently associated with poor outcome (mRS 3-6) and mortality, whereas favorable outcome (mRS 0-2) was observed in 77 (46%), 5 (13%), and 3 (6%) patients with CED 1, 2, and 3, respectively. Anti-edema treatment was considered necessary and administered to 49/260 (19%) patients; only five had favorable outcome. Cerebral edema is frequent (28%) among thrombolysis-treated ischemic stroke patients, occurring in severe forms in 10%. Higher baseline National Institutes of Health Stroke Scale, presence of hyperdense cerebral artery sign or early infarct signs, and longer treatment delays are associated with edema development. Edema is a strong independent predictor of three-month outcome. Effect of anti-edema treatment was modest.

Outcome of Patients with Ductal Carcinoma In Situ and Sentinel Node Biopsy

In sentinel node biopsy (SNB), tumor-positive findings, mainly micrometastases and isolated tumor cells (ITC) have been found in up to 8%-16% of patients with pure ductal carcinoma in situ (DCIS) or microinvasive DCIS (DCISM). The prognostic significance of such findings is largely unknown. The aim of this study is to examine the outcome of DCIS and DCISM patients with SNB. A total of 280 breast cancer patients with pure or microinvasive DCIS underwent SNB between April 2001 and December 2010 at the Breast Surgery Unit of Helsinki University Central Hospital. Patient, tumor, SNB procedure, and follow-up data were gathered. The median follow-up was 50months (range 7-123months). Altogether, 21 patients had tumor-positive sentinel node findings. Of these, 14 were in pure DCIS patients (1 macrometastasis, 1 micrometastasis, 12 ITC) and 7 in DCISM patients (1 macrometastasis, 2 micrometastases, 4 ITC). Also, 16 patients, 10 with pure DCIS and 6 with DCISM, underwent completion axillary lymph node dissection (ALND). Only 1 of them, a patient with DCISM, had additional tumor positive finding in the ALND. During a median follow-up of 50months (range 7-123months) there were 5 local recurrences. One patient with pure DCIS and tumor-negative SNB developed overt axillary metastases and later also distant metastases. DCIS and DCISM patients do have tumor positive findings, but a majority of these are ITC or micrometastases. In light of this study, these findings do not affect the outcome of DCIS or DCISM patients.

CIP2A overexpression is associated with c-Myc expression in colorectal cancer

Background: To improve the prognostic evaluation of colorectal cancer requires new molecular markers. Cancerous inhibitor of protein phosphatase 2A (CIP2A) serves as an oncoprotein by targeting PP2A-mediated inhibition of c-Myc. A prognostic role for CIP2A has been demonstrated in gastric, lung, and tongue cancers. Methods: 863 consecutive colorectal cancer patients treated at Helsinki University Central Hospital in 1983-2001 were collected with 752 scored successfully for CIP2A immunohistochemical expression from tumor tissue microarrays. Associations with clinicopathologic variables and molecular markers were explored by the chi-square test, and the Kaplan-Meier method served for survival analysis. Results: CIP2A was overexpressed in 661 (87.9%) specimens. CIP2A overexpression was associated with tumor differentiation grade (p = 0.014), p53 immunopositivity (p = 0.042), EGFR immunopositivity (p = 0.007), and c-Myc nuclear immunopositivity (p = 0.018). In survival analysis, CIP2A failed to show any prognostic significance (p = 0.270, log-rank test). Conclusions: Overexpression of CIP2A in colorectal cancer patients may be an important step in colorectal carcinogenesis. Based on our findings, CIP2A shows no association with patient prognosis in colorectal cancer, but is associated with nuclear c-Myc.

Does non‐curative gastrectomy improve survival in patients with metastatic gastric cancer?

The role of non-curative or palliative gastrectomy remains controversial. Our aim was to compare retrospective patients who have undergone non-curative gastrectomy to the patients with surgical exploration only. Between years 2000 and 2009, 488 patients with gastric adenocarcinoma were treated at the Department of Surgery, Helsinki University Central Hospital. Fifty-five patients had metastatic disease but their symptoms were not severe enough to require palliative surgery. Thirty-two of them underwent operative exploration (Group A), and 23 non-curative gastrectomy (Group B). All operations were initiated with curative intent. The difference in median survival between Groups A and B was insignificant (5.7 months in Group A and 10.8 months in Group B, P = 0.152). However, 33 patients with postoperative chemotherapy had significantly better median survival than the others (14.2 months vs. 1.9 months, P < 0.001). No significant differences were observed between Groups A and B in the rate of late postoperative gastrointestinal obstruction or bleeding. Non-curative gastrectomy does not improve survival in patients with metastatic gastric cancer, nor reduces the rate of late occlusions. There is no need for prophylactic palliative gastrectomy in patients with gastric cancer who do not have bleeding or obstruction preoperatively. Among those patients, postoperative chemotherapy seems to improve survival.

A web-based prognostic tool for extremity and trunk wall soft tissue sarcomas and its external validation

Background:We developed a web-based, prognostic tool for extremity and trunk wall soft tissue sarcoma to predict 10-year sarcoma-specific survival. External validation was performed.Methods:Patients referred during 1987–2002 to Helsinki University Central Hospital are included. External validation was obtained from the Lund University Hospital register. Cox proportional hazards models were fitted with the Helsinki data. The previously described model (SIN) includes size, necrosis, and vascular invasion. The extended model (SAM) includes the SIN factors and in addition depth, location, grade, and size on a continuous scale. Models were statistically compared according to accuracy (area under the ROC curve=AUC) of 10-year sarcoma-specific survival prediction.Results:The AUC of the SAM model in10-year survival prediction in the Helsinki patient series was 0.81 as compared with 0.74 for the SIN model (P=0.0007). The corresponding AUCs in the external validation series were 0.77 for the SAM model and 0.73 for the SIN model (P=0.03). A web-based calculator for the SAM model is available at http://www.prognomics.org/sam.Conclusion:Addition of grade, depth, and location as well as tumour size on a continuous scale significantly improved the accuracy of the prognostic model when compared with a model that includes only size, necrosis, and vascular invasion.

Predicting outcome of IV thrombolysis–treated ischemic stroke patients

To develop a functional outcome prediction score, based on immediate pretreatment parameters, in ischemic stroke patients receiving IV alteplase. The derivation cohort consists of 1,319 ischemic stroke patients treated with IV alteplase at the Helsinki University Central Hospital, Helsinki, Finland. We evaluated the predictive value of parameters associated with the 3-month outcome and developed the score according to the magnitude of logistic regression coefficients. We assessed accuracy of the model with bootstrapping. External validation was performed in a cohort of 330 patients treated at the University Hospital Basel, Basel, Switzerland. We assessed the score performance with area under the receiver operating characteristic curve (AUC-ROC). The DRAGON score (0-10 points) consists of (hyper)Dense cerebral artery sign/early infarct signs on admission CT scan (both = 2, either = 1, none = 0), prestroke modified Rankin Scale (mRS) score >1 (yes = 1), Age (≥ 80 years = 2, 65-79 years = 1, <65 years = 0), Glucose level at baseline (>8 mmol/L [>144 mg/dL] = 1), Onset-to-treatment time (>90 minutes = 1), and baseline National Institutes of Health Stroke Scale score (>15 = 3, 10-15 = 2, 5-9 = 1, 0-4 = 0). AUC-ROC was 0.84 (0.80-0.87) in the derivation cohort and 0.80 (0.74-0.86) in the validation cohort. Proportions of patients with good outcome (mRS score 0-2) were 96%, 88%, 74%, and 0% for 0-1, 2, 3, and 8-10 points, respectively. Proportions of patients with miserable outcome (mRS score 5-6) were 0%, 2%, 5%, 70%, and 100% for 0-1, 2, 3, 8, and 9-10 points, respectively. External validation showed similar results. The DRAGON score is valid at our site and was reliable externally. It can support clinical decision-making, especially when invasive add-on strategies are considered. The score was not studied in patients with basilar artery occlusion. Further external validation is warranted.

Intravenous thrombolysis in ischemic stroke patients with isolated homonymous hemianopia

Patients with posterior ischemic stroke were usually excluded from thrombolytic treatment in clinical trials and clinical practice, and little is known about effectiveness of thrombolysis treatment in such patients who may end up with severe disability. We aimed to describe the outcome of acute ischemic stroke patients presenting with isolated homonymous hemianopia and treated with intravenous thrombolysis. A case report of three patients presenting with homonymous hemianopia owing to posterior circulation stroke treated with intravenous thrombolysis at the Helsinki University Central Hospital. Main outcome measures were modified Rankin Scale and neuropsychological examination at 3months after thrombolysis. We further evaluated Goldmann visual field examination at 6months. No acute findings appeared on admission non-contrast head-computed tomography scan. All patients had a perfusion deficit on admission-computed tomography perfusion imaging. All patients scored 0 on 3-month modified Rankin Scale, and their neuropsychological evaluation was normal. Goldmann examination revealed no visual field deficit in both female patients, and a modest visual field defect was detected in the male patient. Our experience encourages application of intravenous thrombolytic treatment (especially when supported with multimodality neuroimaging) in patients with homonymous hemianopia, for which rehabilitation options are limited.

Abstract 67: Risk of Symptomatic Intracerebral Hemorrhage in Ischemic Stroke Thrombolysis: the SEDAN Score

Objectives To develop a score for assessing the risk of symptomatic intracerebral hemorrhage (sICH) in ischemic stroke patients treated with iv thrombolysis. Methods The score was derived from a cohort of acute ischemic stroke patients treated with iv thrombolysis (n=972) at the Helsinki University Central Hospital (1995-2008). The predictive value of parameters associated with development of sICH (ECASS-2 criteria) was evaluated, and the score was developed according to the magnitude of logistic regression coefficients. The accuracy of the model was evaluated with 1000 bootstrap replicates. To test the performance of the score, we calculated area under receiver operating characteristic curve (AUC-ROC). We calculated absolute risks and likelihood ratios of sICH per increasing score points. The score was validated externally in merged cohort from 3 Swiss cities (Lausanne, Basel, and Geneva) including 828 ischemic stroke patients treated with iv thrombolysis. Findings The SEDAN score (0 to 6 points) consists of blood S ugar (glucose) at baseline [8.1-12.0 mmol/L (145-216 mg/dL)=1; &gt;12.0 mmol/L (&gt;216 mg/dL)=2], E arly infarct signs (yes=1) and (hyper) D ense cerebral artery sign (yes=1) on admission CT scan, A ge (&gt;75=1), and N IH Stroke Scale on admission (&gt;9=1). Accuracy of the score based on 1000 bootstrap replicates was 93.1% (91.4%-94.5%). AUC-ROC was 0.73 (0.67-0.79; p&lt;0.001). Absolute risk for sICH in patients with increasing score points was: 1.4%, 2.9%, 8.5%, 12.2%, 21.7%, and 33.3% for 0, 1, 2, 3, 4, and 5 score points, respectively. Likelihood ratios were 0.19 (0.06-0.59), 0.40 (0.21-0.76), 1.23 (0.85-1.79), 1.85 (1.26-2.72), 3.68 (2.10-6.45), and 5.66 (2.40-13.40), respectively. Absolute risks in external validation were similar (1.0%, 3.5%, 5.1%, 9.2%, 16.9%, and 27.8%, respectively), and AUC-ROC was 0.77 (0.71-0.83; p&lt;0.001). Conclusions The SEDAN score reliably assesses the risk of sICH in iv thrombolysis treated ischemic stroke patients and can support clinical decision-making in the high-risk patients. External validation of the score in the three Swiss cohorts supports its generalizibility.

Lateral Supraorbital Approach Applied to Tuberculum Sellae Meningiomas

Various surgical approaches for the removal of tuberculum sellae meningiomas (TSMs) have previously been described. To assess the reliability and safety of the lateral supraorbital (LSO) approach to remove TSMs. We identified all TSM patients operated on at the Department of Neurosurgery at Helsinki University Central Hospital, Finland, by the senior author (J.H.) using the LSO approach between September 1997 and August 2010. We retrospectively analyzed the clinical data, radiological findings, surgical treatment, histology, and outcome of patients and discuss the operative technique. Apparent complete tumor removal was achieved in 45 patients (87%). Of 42 patients, preexisting visual deficit improved in 22, remained the same in 13, and worsened in 7, and de novo visual deficit occurred in 1 patient. At 3 months post-discharge, 47 patients (90%) had a good recovery, 4 (8%) were moderately disabled, and 1 (2%) died 40 days after surgery of unexplained cardiac arrest. Seven patients (13%) had minimal residual tumors, 2 of which required reoperation. During the median follow-up of 59 months (range, 1-133 months), tumor recurred in 1 of the patients who had undergone a second operation. TSMs of all sizes can be removed via the LSO approach with minimal morbidity and mortality. Low-power or no coagulation is recommended near the optic nerves and the optic chiasm to preserve their vascular support from the internal carotid artery perforators. Our results are comparable to those obtained using more extensive and time-consuming approaches. We recommend the LSO approach to remove TSMs.

Soft tissue sarcoma – a population-based, nationwide study with special emphasis on local control

Background. A prospective diagnostics and treatment protocol for extremity and trunk wall soft tissue sarcoma (STS) was introduced by the Scandinavian Sarcoma Group in 1986 and it was also widely adopted in Finland. We have updated the protocol and made it more detailed at the Helsinki University Central Hospital. We retrospectively compared diagnostics and treatment of STS in a nationwide population-based material to this protocol with special emphasis on local control. Methods. Data for 219 patients with an STS of extremity or trunk wall diagnosed during 1998–2001 was retrieved from the nationwide Finnish Cancer Registry. Histologic review was performed. Treatment centres were divided into high-, intermediate- and low-volume centres based on the number of patients with final surgery during the study period. Results. Significantly more patients were operated with a preoperative histological or cytological diagnosis at high-volume centres. No preoperative diagnosis was a strong predictor for the patient to undergo more than one operation (p < 0.0001). Wide surgical margin was achieved more often at high-volume centres, but in all centre categories a considerable percentage of patients with inadequate surgical margin did not receive adjuvant radiation therapy. Local control at five years was 82% at high-volume centres, 61% at intermediate-volume centres treating highest percentage of deep tumours and 69% at low-volume centres (p = 0.046). Local control improved as the number of patients operated (surgical volume of the centre) increased. Conclusion. The present quality-control study is the first nationwide population-based study to assess diagnostics and treatment of STS. When referred to a specialised sarcoma centre even patients with inadequate surgery can achieve good local control. STS is a rare cancer and its treatment should be centralised in Finland, which has 5.4 million inhabitants and approximately 100 new STSs of extremities and trunk wall annually.

Early microsurgical treatment for spinal hemangioblastomas improves outcome in patients with von Hippel-Lindau disease

Background:Spinal hemangioblastomas (HB) are rare, histologically benign, highly vascularized tumors often associated with von Hippel–Lindau (VHL) disease. The aim of the current study is to demonstrate the benefit of early surgical resection of large spinal HBs in selected asymptomatic patients with VHL.Methods:Seventeen patients underwent microsurgical resection of 20 spinal HBs at the Department of Neurosurgery at Helsinki University Central Hospital (HUCH). Thirteen tumors were in the cervical spine, five in thoracic and one patient had two lumbar lesions. MRI tumor showed an associated syrinx in 16 patients (94%). Tumor volume ranged from 27 to 2730 mm3. Out of 17 patients, 11 (65%) tested positive for VHL in mutation analysis. Five of these patients with tumors ranging from 55 to 720 mm3 were treated prophylactically.Results:Complete tumor resection was performed in 16 patients (94%) who were followed up for a median of 57 months (range 2–165 months). No patient had neurological decline on long-term follow-up. Among the patients with VHL, five patients with preoperative sensorimotor deficits showed improvement of their symptoms but never regained full function. One patient who presented with tetraplegia remained the same. Otherwise, all five patients with prophylactic surgery remained neurologically intact.Conclusion:Although documented growth on serial MRIs and the need for pathological diagnosis have been suggested as indications for surgery in otherwise asymptomatic patients, our series showed that a potentially larger group of asymptomatic patients with spinal HB associated with VHL would benefit from microsurgical resection. Long-term results of the surgical management of spinal HB are generally favorable. Our results suggest staging and early treatment for spinal HB larger than 55 mm3, especially in patients with VHL. Small spinal HBs may be followed up.

P-1010 - JERI - a finnish integrated intervention model for adolescents at risk for psychosis

Introduction Jorvi Early psychosis Recognition and Intervention (JERI) - team at Helsinki University Central Hospital (HUCH) is an early detection and intervention team for adolescents at risk for psychosis. Objectives The JERI team meets with adolescents at ages between 12–22 at school or at home together with their parents and with community co-worker, for example with social worker, teacher, nurse or GP, who has contacted the team for reason of unclear or undiagnosed mental health problems. Aims The main purpose of JERI team is to identify the possible risk of psychosis by interview instruments and meet the client and family together with community co worker(s) to find a way to reduce stress. Methods The model is based on idea of community and family oriented care and stress-vulnerability model of psychosis. The JERI hypothesis is that stress-reducing care where family and community co workers are involved could decrease pre-psychotic symptoms and increase functioning ability in adolescents at risk for psychosis. Results As an example: A school nurse contacts JERI-team because of a schoolboy who has started to stay at home recently. His parents argue a lot, he is bullied at school and he has problems in school performance. The parents would be involved in discussions about the family situation, the school social worker about how to stop bullying and the teacher how to support the school performance despite of possible cognitive problems. Conclusions Presented model seems to work according to clinical experience and an earlier follow-up study.

Treatment of Chronic Rhinosinusitis With Antibiotics

Chronic rhinosinusitis is among the most common chronic diseases. It presents a major financial burden to the health care system [1], not to mention the burden of personal suffering and morbidity to the patient with debilitating chronic rhinosinusitis. Chronic rhinosinusitis is not a uniform entity, and its clinical presentations and etiologies may vary. Environmental factors predispose patients to chronic rhinosinusitis, but allergens for allergic patients or other environmental irritants may be ill defined. Chronic rhinosinusitis may present with nasal polyposis that sometimes occurs in conjunction with asthma and aspirin insensitivity. Traditionally, the disease is classified as chronic rhinosinusitis either with or without polyposis, a distinction that may reflect differences in the cytokines between the 2 conditions. However, the difference between these 2 may not always be clinically obvious because some patients present with polypoid thickening of the mucosa in the middle nasal meatus without obvious nasal polyps. Chronic rhinosinusitis may also occur with comorbidities other than allergy and asthma, such as immune deficiencies and disorders of the mucociliary clearance. Because of the variability of the etiology of chronic rhinosinusitis, it is challenging to define. The American Academy of Otolaryngology—Head and Neck Surgery published in 2007 a clinical practice guideline that defines chronic rhinosinusitis by clinical signs, symptoms, and objective findings [2]. According to the guideline, chronic rhinosinusitis is defined by having for 12 weeks or longer$2 of the following signs and symptoms: (1) mucopurulent drainage (anterior, posterior, or both); (2) nasal obstruction (congestion); (3) facial pain, pressure, or fullness; or (4) decreased sense of smell. In addition, objective findings of nasal inflammation are needed for the diagnosis. These are $1 of the following: (1) purulent (not clear) mucus or edema in the middle meatus or ethmoid region, (2) polyps in the nasal cavity or the middle meatus, or (3) radiographic imaging showing inflammation of the paranasal sinuses. In an office setting, the first 2 findings can be evaluated by nasal endoscopy. The preceding definition of chronic rhinosinusitis requires neither a microbiologic diagnosis nor the isolation of a pathogen in the nasal sinuses. For example, at present it is often unknown in a given patient whether nasal polyposis is actually triggered by a microbe, microbial superantigen, or an environmental agent, or whether there is any foreign triggering agent in the first place. Nevertheless, chronic rhinosinusitis may involve biofilm formation that is accompanied by acute exacerbations of sinus infection [3]. The cornerstones of treatment of chronic rhinosinusitis are relief of inflammation of the nasal mucosa, facilitation of drainage of secretions, and if possible, restoration of mucociliary clearance within the sinuses [4]. The rationale in relieving inflammation is to reduce swelling of the mucosa, which may then open obstructed sinus cavities and improve drainage. Topical corticosteroids are widely used for this purpose. Short courses of oral steroids are used to reduce the size of nasal polyps and in selected cases to relieve overt inflammation in the nasal mucosa. Saline nasal irrigation is also widely used in patients with chronic rhinosinusitis [5]. Self-administered saline irrigation helps to remove crusts, mucus, and irritants. Many patients report that saline irrigation improves their symptoms. It follows that an ideal treatment for a biofilm disease would be to remove the biofilm mechanically, which could at least to some extent be accomplished by saline irrigation. Endoscopic sinus surgery is reserved for patients who fail to benefit from medical therapy. Here again the aim is often to improve drainage from the nasal sinuses. A common reason for surgery is to remove nasal polyps that do not respond to medical therapy. Received 31 August 2011; accepted 6 September 2011; electronically published 22 November 2011. Correspondence: Petri Mattila, MD, PhD, Department of Otorhinolaryngology, Helsinki University Central Hospital, PO Box 220, FI-00029 HUS, Helsinki, Finland (petri.mattila@hus.fi). Clinical Infectious Diseases 2012;54(1):69–70 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cir757

Prognostic significance of matrix metalloproteinase‐2, ‐8, ‐9, and ‐13 in oral tongue cancer

Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring. Seventy-three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992-2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)-2, -8, -9, and -13 was compared with patient characteristics and outcome. Nuclear expression of MMP-13, but not cytoplasmic expression of MMP-2, -8, and -9, was associated with invasion depth (P = 0.017) and tumor size (P = 0.008). Furthermore, high nuclear MMP-13 expression was predictive of poor outcome (P = 0.042). Our results suggest that especially MMP-13 may be regarded as a prognostic biomarker in OTSCC.

Clinical characteristics of patients with Epstein Barr virus in cerebrospinal fluid

BackgroundThe role of Epstein-Barr (EBV) virus in central nervous system (CNS) infections is not fully resolved. It is clearly associated with lymphoproliferative disease of immunosuppressed persons, and may cause encephalitis.MethodsWe reviewed the medical records, imaging and laboratory findings of all patients EBV DNA PCR positive in cerebrospinal fluid (CSF) during 2000 to 2009 in the Helsinki University Central Hospital.ResultsWe identified 32 patients with EBV DNA in CSF. 11 had history of allogeneic hematopoietic stem cell transplantation, 7 solid organ transplantation and 5 HIV/AIDS. 5 patients had no preceding immunodeficiency.In 8 of the cases, another pathogen was identified in CSF. These were M. tuberculosis (2), T. gondii (2), Aspergillus (1), Herpes simplex virus 1 (1), C. neoformans (1) and Human herpesvirus 6 (1). Altogether in 15/32 (47%) of the cases the clinician had a strong suspicion of cause other than EBV for the patients' CNS symptoms/findings.Of note, 7 of 11 (64%) patients with stem cell transplantation had encephalitis (univariate odds ratio 5.6; confidence Interval 1.1-27.4). Of these 6 had no other pathogen identified.ConclusionsEBV DNA was often found together with other microbial findings in CSF of immunocompromised patients. EBV seems to be associated with encephalitis in stem cell transplant recipients.

Genetic background and the risk of otitis media

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.

Periodontitis is associated with angiographically verified coronary artery disease

We investigated the association of periodontitis and severity of coronary artery disease (CAD) as verified using coronary angiography. Participants were recruited among those attending coronary angiography at Helsinki University Central Hospital, Finland, in 2007 and 2008. Detailed clinical periodontal examination [number of teeth, bleeding on probing, periodontal probing depth (PPD)] and oral panoramic radiographs [alveolar bone loss (ABL), angular bone defects] were performed. Of 506 patients, 123 (24.3%) had no significant CAD, whereas 184 (36.4%) had stable CAD and 169 (33.4%) acute coronary syndrome (ACS). Both stable CAD and ACS were associated with 8-17 missing teeth with ORs 4.33 (1.61-11.7, p=0.020) and 5.24 (1.90-14.5, p=0.014), and more than seven teeth with PPD ≥6mm with ORs 2.44 (1.01-6.07, p=0.049) and 2.75 (1.16-6.53, p=0.022) respectively. Severe ABL was associated with ACS with an OR 5.39 (1.23-23.6, p=0.025). Number of stenosed arteries was linearly associated with ABL (p for trend <0.001), number of missing teeth (p<0.001), and pockets with probing depth ≥6mm (p=0.033). Compared with patients with no significant stenosis, poor periodontal health including missing teeth, periodontal inflammation, and bone loss is associated with angiographically verified coronary artery narrowing in patients with stable CAD or ACS.