Imre Ilves

Randomized Multicenter Trial Comparing Glue Fixation, Self-gripping Mesh, and Suture Fixation of Mesh in Lichtenstein Hernia Repair (FinnMesh Study).

OBJECTIVE Three different mesh fixation techniques were compared to find out how to perform a safe and cost-effective open inguinal hernioplasty in day-case setting with the best outcomes with regard to chronic pain. SUMMARY BACKGROUND DATA Mesh fixation method may influence on the incidence of chronic pain after Lichtenstein hernioplasty. METHODS Lichtenstein hernioplasty was performed under local anesthesia in 625 patients as day-case surgery in 8 Finnish hospitals. The patients were randomized to receive either a cyanoacrylate glue (Histoacryl, n = 216), self-gripping mesh (Parietex ProGrip, n = 202), or conventional nonabsorbable sutures (Prolene 2-0, n = 207) for mesh fixation. The incidence of wound complications, pain, recurrences, and patients discomfort was recorded on days 1, 7, 30, and 1 year after surgery. The primary endpoint was the sensation of pain measured by pain scores and the need of analgesics after 1 year of surgery. RESULTS The type and size of inguinal hernias were similar in the 3 study groups. The duration of operation was 34 ± 13, 32 ± 9, and 38 ± 9 minutes in the glue, self-gripping, and suture groups, respectively (P < 0.001). There were no significant differences postoperatively in pain response or need for analgesics between the study groups. Two superficial infections (0.3%), 31 wound seromas (5.0%), and 4 recurrent hernias (0.6%) were recorded during a 1-year follow-up. Some 25 patients (4.2%) needed occasionally analgesics for chronic groin pain. A feeling of a foreign object and quality of life were similar in all study groups. CONCLUSIONS This randomized trial failed to prove that mesh fixation without sutures causes less inguinodynia than suture fixation in Lichtenstein hernioplasty. Mesh fixation without sutures is feasible without compromising postoperative outcome.

Seasonal variations of acute appendicitis and nonspecific abdominal pain in Finland

AIM To investigate whether seasonal changes had an effect on the incidence of acute appendicitis (AA) or nonspecific abdominal pain (NSAP). METHODS We carried out a national register study of all patients with a hospital discharge diagnosis of AA and acute NSAP in Finland. Data were analyzed for the whole country and correlated to seasonal and weather parameters (temperature, humidity). Moreover, additional sub-analyses were performed for five geographically different area of Finland. RESULTS The observation period spanned 21 years, with 186558 appendectomies, of which 137528 (74%) cases were reported as AA. The incidence of AA declined for 32% over the study period. The average incidence of the NSAP was 34/10000 per year. The mean annual temperature, but not relative humidity, showed clear geographical variations. The incidence of AA decreased significantly during the cold months of the year. No correlation was detected between temperature and incidence of NSAP. Humidity had a statistically significant impact on NSAP. CONCLUSION The incidence of acute appendicitis is declining in Finland. We detected a clear seasonality in the incidence of AA and NSAP.

Genetic Risk Score Does Not Predict the Outcome of Obesity Surgery

BackgroundWe evaluated the benefit of using combined genetic risk score (GRS) of known single nucleotide polymorphisms (SNPs) for body mass index (BMI) and waist/hip ratio (WHR) in the prediction of weight loss and weight regain after obesity surgery.MethodsA total of 163 consecutive morbidly obese individuals undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in a single bariatric center in Finland were recruited. Fasting blood samples were drawn after 12 h of fasting before and 1 year after bariatric operation. Data for weight regain and medication were collected with a questionnaire after 3.1 ± 2.7 years (mean ± SD) follow-up. Nonalcoholic steatohepatitis (NASH) was diagnosed with liver histology. Twenty BMI- and 13 WHR-related SNPs were genotyped. Linear regression was used to identify factors predicting weight loss and weight regain.ResultsLower baseline BMI predicted greater decline in BMI (p = 0.0005) and excess weight loss (EWL) (p = 0.009). In the multiple linear regression analysis age and BMI, explained the variance of EWL during the first year while GRS, sex, fasting plasma glucose, serum insulin and NASH diagnosis did not have any effect. None of the baseline clinical variables explained BMI regain. The combined GRS did not associate with weight or BMI at baseline, with 1-year changes or with weight regain between 1 year and an average of 3.1 years follow-up.ConclusionsIn our study, we found that the genotype risk score does not predict weight loss after obesity surgery while lower baseline BMI predicted the greater weight loss.

Adipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss

Aims/hypothesisThe insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue.MethodsTo determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n = 108) and a very low calorie diet (VLCD) intervention (n = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n = 49).ResultsExpression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery (p = 1 × 10−5) and the VLCD (p = 1 × 10−4). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies (p = 3 × 10−22). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 (p = 1 × 10−5), a known regulator of INSR exon 11 splicing.Conclusions/interpretationINSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.

Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis

Appendicitis represents a common and severe gastrointestinal illness in younger individuals worldwide. The disease is characterized by an excessive inflammatory response and it is believed that bacterial overgrowth due to blockage of the appendix lumen might be involved. Despite the high incidence, only limited data on the pathophysiological changes exist; in particular, the innate immune responses involved are largely unknown. Real-time PCR analysis of tissue samples from inflamed and normal appendices demonstrated differentially regulated expression patterns of epithelial-derived antimicrobial peptides (AMP). The α-defensins human neutrophil peptides 1–3, HD5 and HD6, as well as the two β-defensins, human β-defensins (hBD)-2 and hBD-3, were up-regulated, whereas hBD-1 was down-regulated in acute appendicitis. Expression of upstream regulators of AMP expression, NOD-2 and TLRs 1, 2, 4, 5, 7, 8 and 10 was significantly increased as detected by real-time PCR. Finally, we confirmed the involvement of the pro-inflammatory cytokines IL-1β and IL-8, and detected characteristic changes in microbial community composition in appendicitis tissue specimens by 16S rDNA based detection techniques. In this study, we demonstrate a differential regulation of the innate immune system along with an altered bacterial diversity in acute appendicitis.

Regulation of alternative splicing in human obesity loci.

Multiple obesity susceptibility loci have been identified by genome‐wide association studies, yet the mechanisms by which these loci influence obesity remain unclear. Alternative splicing could contribute to obesity by regulating the transcriptomic and proteomic diversity of genes in these loci.

Outpatient Antibiotic Use and the Incidence of Acute Appendicitis in Finland: A Nationwide Study from 1990–2008

BACKGROUND The incidence of acute appendicitis (AA) has decreased in Finland. We hypothesized that changing trends in outpatient antibiotic use might explain at least part of this declining incidence of AA. METHODS The number of all patients with AA in Finland was extracted from the national data base from 1990 to 2008. For comparison, the incidence of acute diverticulitis of the colon (AD) was also recorded. All outpatient prescriptions of antibiotics belonging to the major groups of these drugs were also recorded. We used unit root and co-integration analyses for statistical analysis of the data in the study. RESULTS The incidence of AA in Finland declined from 14.5 to 9.8 per 10,000 inhabitants (32%) and the incidence of AD increased by 47% between 1993 and 2007. The total outpatient use of antibiotics did not increase during this same period, but the use of antibiotics effective widely against colonic pathogens (macrolides, fluoroquinolones, and cephalosporins) increased significantly. No correlation was found between the incidence of AA, that of AD, and the use of different groups of antibiotics. CONCLUSIONS Our nationwide registry study indicated that changes in outpatient antibiotic use do not explain the decreasing trend in AA in Finland. Other factors, such as improved diagnosis of AA, may have some role in the decreasing incidence of AA.

Clinical and laboratory findings in the diagnosis of right lower quadrant abdominal pain: outcome analysis of the APPAC trial.

Abstract Background: The current research on acute appendicitis aims to improve the diagnostics and to clarify to whom antibiotic treatment might be the treatment of choice. Methods: The present study is a retrospective analysis of a prospectively collected data in our randomized multicenter trial comparing surgery and antibiotic treatment for acute uncomplicated appendicitis (APPAC trial, NCTO1022567). We evaluated 1321 patients with a clinical suspicion of acute appendicitis, who underwent computed tomography (CT). Age, gender, body temperature, pain scores, the duration of symptoms, white blood cell count (WBC) and C-reactive protein (CRP) were recorded on admission. Results: CT confirmed the diagnosis of acute appendicitis in 73% (n=970) and in 27% (n=351) it revealed no or other diagnosis. Acute appendicitis patients had significantly higher WBC levels than patients without appendicitis (median 12.2 and 10.0, respectively, p<0.0001), whereas CRP levels did not differ between the two groups. Ideal cut-off points were assessed with receiver operating characteristic (ROC) curves, but neither these markers or neither their combination nor any clinical characteristic could accurately differentiate between patients with acute appendicitis and those without. The proportion of patients with normal WBC count and CRP was significantly (p=0.0007) lower in patients with acute appendicitis than in patients without appendicitis. Conclusions: Both clinical findings and laboratory tests are unable to reliably distinguish between patients with acute appendicitis and those without. If both WBC count and CRP are normal, acute appendicitis is very unlikely. The current results emphasize the role of CT imaging in patients with suspected acute appendicitis.