Heini Huhtala

Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 cases.

BACKGROUND Clinical studies have revealed a number of important risk factors for postoperative infection following total knee arthroplasty. Because of the small numbers of cases in those studies, there is a risk of obtaining false-negative results in statistical analyses. The purpose of the present study was to determine the risk factors for infection following primary and revision knee replacement in a large register-based series. METHODS A total of 43,149 primary and revision knee arthroplasties, registered in the Finnish Arthroplasty Register, were followed for a median of three years. The Finnish Arthroplasty Register and the Finnish Hospital Discharge Register were searched for surgical interventions that were performed for the treatment of deep postoperative infections. Cox regression analysis with any reoperation performed for the treatment of infection as the end point was performed to determine the risk factors for this adverse outcome. RESULTS Three hundred and eighty-seven reoperations were performed because of infection. Both partial and complete revision total knee arthroplasty increased the risk of infection as compared with the risk following primary knee replacement. Male patients, patients with seropositive rheumatoid arthritis or with a previous fracture around the knee, and patients with constrained and hinged prostheses had increased rates of infection after primary arthroplasty. Wound-related complications increased the risk of deep infection. The rate of septic failure was lower after unicondylar than after total condylar primary knee arthroplasty, but the difference was not significant. The combination of parenteral antibiotic prophylaxis and prosthetic fixation with antibiotic-impregnated cement protected against septic failure, especially after revision knee arthroplasty. Following revision total knee arthroplasty, diagnosis and prosthesis type had no effect, but previous revision for the treatment of infection and wound-healing problems predisposed to repeat revision for the treatment of infection. CONCLUSIONS There was an increased risk of deep postoperative infection in male patients and in patients with rheumatoid arthritis or a fracture around the knee as the underlying diagnosis for knee replacement. The results of the present study suggest that the infection rate is similar after partial revision and complete revision total knee arthroplasties. Combining intravenous antibiotic prophylaxis with antibiotic-impregnated cement seems advisable in revision arthroplasty.

Nocturia Frequency, Bother, and Quality of Life: How Often Is Too Often? A Population-Based Study in Finland

BACKGROUND Nocturia (ie, waking at night to void) is common and disrupts sleep. Traditionally, one nightly episode has been regarded as clinically meaningless, yet the justification for this belief remains weak. OBJECTIVE To evaluate the association among frequency of nocturia and bother and health-related quality of life (HRQoL). DESIGN, SETTING, AND PARTICIPANTS In 2003-2004, a survey was mailed to a random sample of 6000 subjects aged 18-79 yr who were identified from the Finnish Population Register Centre (response proportion was 62.4%; 53.7% were females). MEASUREMENTS HRQoL and bother from nocturia were examined in relation to self-reported nocturia frequency (using the American Urological Association Symptom Index and the Danish Prostatic Symptom Score). Bother from nocturia was assessed on a four-point scale (none, small, moderate, major). HRQoL was measured with the generic 15D instrument on a 0-1 scale with a minimum clinically important difference of 0.03. RESULTS AND LIMITATIONS Degree of bother increased with nocturia frequency (p<0.01). The most commonly cited degree of bother for those with one, two, and three nightly voids was no bother, small bother, and moderate bother, respectively. The mean age-adjusted 15D score for men (and women) without nocturia was 0.953 (0.950) and 0.925 (0.927) with one void per night, 0.898 (0.890) with two voids per night, and 0.833 (0.840) with three or more voids per night. Statistically significant decreases were found in 15D score and in all 15D dimensions except eating. Although the response rate was high, approximately one third of those contacted did not participate in the study. CONCLUSIONS At least two voids per night is associated with impaired HRQoL. The majority of people report having bother when the number of nocturia episodes is two and moderate or major bother when the number is three or more. One void per night does not identify subjects with interference from nocturia and, thus, is not a suitable criterion for clinically relevant nocturia.

Diagnosing Mild Enteropathy Celiac Disease: A Randomized, Controlled Clinical Study

BACKGROUND & AIMS The diagnostic criteria for celiac disease require small-bowel mucosal villous atrophy with crypt hyperplasia (Marsh III). However, mucosal damage develops gradually and patients may evince clinical symptoms before histologic changes appear. Endomysial antibodies are specific in predicting forthcoming villous atrophy. We hypothesized that patients with mild enteropathy but positive endomysial antibodies benefit from a gluten-free diet (GFD) similarly to patients with more severe enteropathy. METHODS Small-bowel endoscopy together with clinical evaluations was performed in all together 70 consecutive adults with positive endomysial antibodies. Of these, 23 had only mild enteropathy (Marsh I-II) and they were randomized either to continue on a gluten-containing diet or start a GFD. After 1 year, clinical, serologic, and histologic evaluations were repeated. A total of 47 participants had small-bowel mucosal lesions compatible with celiac disease (Marsh III), and these served as disease controls. RESULTS In the gluten-containing diet group (Marsh I-II) the small-bowel mucosal villous architecture deteriorated in all participants, and the symptoms and abnormal antibody titers persisted. In contrast, in the GFD group (Marsh I-II) the symptoms were alleviated, antibody titers decreased, and mucosal inflammation diminished equally to celiac controls (Marsh III). When the trial was completed, all participants chose to continue on a life-long GFD. CONCLUSIONS Patients with endomysial antibodies benefit from a GFD regardless of the degree of enteropathy. The diagnostic criteria for celiac disease need re-evaluation: endomysial antibody positivity without atrophy belongs to the spectrum of genetic gluten intolerance, and warrants dietary treatment.

Apolipoprotein E―Dependent Accumulation of Alzheimer Disease―Related Lesions Begins in Middle Age

To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community‐dwelling normal population.

Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits

Background: Some patients with untreated coeliac disease are negative for serum endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). Aims: To evaluate the clinical and histological features of EmA-negative coeliac disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be seen in the small-bowel mucosa when absent in serum. Patients: Serum EmA was studied in 177 biopsy-proved specimens from adult patients with coeliac disease. 20 patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. Methods: Clinical manifestations, small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA-negative and EmA-positive patients. Results: 22 patients with IgA-competent coeliac disease were negative for serum EmA. Three of these had small-bowel lymphoma. Patients with EmA-negative coeliac disease were older, had abdominal symptoms more often, and the density of γδ+ intraepithelial lymphocytes in their intestinal mucosa was lower than in EmA-positive patients; otherwise the histology was similar. All serum EmA-negative patients with coeliac disease, but none of the disease controls, had gluten-dependent mucosal IgA deposits alongside TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be TG2-specific by its ability to bind recombinant TG2. Conclusions: Negative serum EmA might be associated with advanced coeliac disease. TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative coeliac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and coeliac disease.

Incidence of inflammatory bowel disease in finnish children, 1987–2003

Background: The incidence of inflammatory bowel disease (IBD) has been increasing in Western countries. In younger people, Crohns disease (CD) predominates over ulcerative colitis (UC), but the finding is not universal. The present study aimed to characterize not only the incidence but also the clinical picture of IBD from 1987 to 2003 in a large pediatric population in Finland. Materials and Methods: Data were collected from the patient discharge and medical records at the 2 largest university hospitals in Finland. The study population covered a total of 619,340 children, representing 56% of the children <18 years old in the country. All of the cases diagnosed with IBD from 1987 to 2003 were reviewed. Clinical, endoscopic, and histological data were collected. Incidence rates were estimated based on statistical assumptions. Results: A total of 604 cases with IBD were diagnosed during the 17‐year period. All of the patients had undergone endoscopy. The diagnosis was CD in 203 (34%) cases, UC in 317 (52%) cases, and indeterminate colitis (IC) in 83 (14%) cases. The mean annual incidence rate increased from 3.9/100,000 (95% confidence interval [CI] 2.5–5.8) in 1987 to 7.0/100,000 (CI 5.0–9.4) in 2003 (P < 0.001). The majority of cases were 12 to <15 years old (n = 200, 33%). Of the patients, 5.1% were <3 years old and 14% were <6 years old. IC was most common in young children; 29% of all IBD patients <3 years of age had IC. Of the patients, 97% had been followed up until the age 18 in the hospitals after initial diagnosis (median follow‐up 3.1 years). Of the patients, 45.2% were initially treated with steroids, whereas 17.8% received immunosuppressive agents at the end of the follow‐up. Operations had been performed in 21% of the cases before age 18. The median time interval from the diagnosis to the first operation was 1.8 (range 7.8) years. Conclusions: The incidence of pediatric IBD almost doubled in Finland from 1987 to 2003. Surgical intervention was common early in the disease course.

Serum-free, xeno-free culture media maintain the proliferation rate and multipotentiality of adipose stem cells in vitro

BACKGROUND AIMS Human adipose stem cells (ASC) are an abundant, readily available population of multipotent progenitor cells that reside in adipose tissue. ASC have been shown to have therapeutic applicability in pre-clinical studies, but a standardized expansion method for clinical cell therapy has yet to be established. Isolated ASC are typically expanded in medium containing fetal bovine serum (FBS); however, sera and other culturing reagents of animal origin in clinical therapy pose numerous safety issues, including possible infections and severe immune reactions. METHODS To identify optimal conditions for ex vivo expansion of ASC, the effects of seven serum-free (SF) and xeno-free (XF) media were investigated with both FBS and allogeneic human serum (alloHS; as a control media). Surface marker expression, proliferation, morphology and differentiation analyzes were utilized for investigating the effects of media on ASC. RESULTS The proliferation and morphology analysis demonstrated significant differences between ASC cultured in SF/XF culture media compared with serum-containing culture media, with medium prototype StemPro MSC SFM XenoFree providing significantly higher proliferation rates than ASC cultured in media containing serum, while still maintaining the differentiation potential and surface marker expression profile characteristic of ASC. CONCLUSIONS Looking forward, fully defined XF media formulations will provide the means for the development and approval of safer clinical cell therapy treatments. However, to fully recognize the capacity of these XF culture media, further pre-clinical safety and efficacy studies must be performed.

Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease

Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease.

Is nocturia equally common among men and women? A population based study in Finland

PURPOSE We assessed the prevalence of nocturia and its association with sociodemographic factors. MATERIALS AND METHODS Information was collected with a questionnaire mailed to a random sample of 6,000 subjects 18 to 79 years old, identified from the Finnish Population Register Centre. Nocturia was defined as 1 or more, or 2 or more voids per night. Information was collected using the DAN-PSS questionnaire with an additional question from the AUA-SI questionnaire. Age standardized prevalence was calculated using the European standard population. Logistic regression was used for multivariate analysis. RESULTS Of the 6,000 subjects 62.4% responded and 97.9% of the participants provided information on all nocturia questions. The age standardized prevalence of nocturia (1 or more voids per night) was 37% (95% CI 34%-40%) among men and 43% (95% CI 40%-46%) among women. With criterion of 2 or more voids per night prevalence was 12% (95% CI 10%-14%) for men and 13% (95% CI 11%-14%) for women. Women 18 to 49 years old had more nocturia than men. At 50 to 59 years old half of men and women reported nocturia. In older age groups nocturia was more frequent among men than women. The prevalence of nocturia increased at a constant rate with age. It increased twice as rapidly in men as among women (increase in OR 7.3% [95% CI 6.5%-8.2%] and 3.5% [95% CI 2.9%-4.1%] per year among men and women, respectively). CONCLUSIONS The age standardized prevalence of nocturia (1 or more voids per night) was approximately 40% for both genders. In men the prevalence of nocturia increases more rapidly with age than in women. Nocturia is more common among women at a younger age but the differences disappear by middle age. In the elderly nocturia is more frequent among men.

Coeliac Disease, autoimmune diseases and gluten exposure

Objective Gluten-free diet treatment has been proposed to prevent the development of autoimmune diseases in coeliac subjects. The aim here was to investigate the occurrence of autoimmune disorders in relation to gluten intake in coeliac patients in a well-defined area. Material and methods The frequency of autoimmune disorders was evaluated in 703 adults and children with coeliac disease and in 299 controls with normal duodenal histology. Incidence figures were given per 10,000 person-years. In logistic regression analysis, where the prevalence of autoimmune disorders was a dependent variable, the effect of age at end of follow-up, age at diagnosis of coeliac disease, actual gluten exposure time, gender and diagnostic delay were assessed. Results The prevalence of autoimmune diseases was significantly higher in coeliac subjects than in controls. In logistic regression analysis, age at end of follow-up, age at diagnosis of coeliac disease and female gender increased the risk of autoimmune disorders, whereas actual gluten exposure time reduced the risk; diagnostic delay had no effect. A similar, though not statistically significant, trend was seen in childhood coeliac disease to that in the whole study group. Conclusions Despite that fact that patients with coeliac disease are at increased risk of various autoimmune conditions, the duration of gluten exposure seems not to be of crucial importance in the development of autoimmune diseases.