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Background This was a prospective, multicentre, non-blinded, randomized clinical trial involving two parallel groups of patients. Methods Adult patients with symptomatic unilateral primary inguinal hernia were included in this study. Patients were enrolled and treated in five Finnish hospitals. Eligible patients were randomized by use of a computer-based program to receiving either open anterior repair (modified Lichtenstein) with glue mesh fixation or totally extraperitoneal (TEP) repair. The primary aims were to compare 30-day patient-reported pain scores and return to work after surgery between the two groups. Results A total of 202 patients were randomized: 98 patients to TEP repair and 104 patients to open repair. All randomized patients received their allocated treatment. A total of 86 patients (88 per cent) in the TEP group and 94 patients (90 per cent) in the Lichtenstein group completed the 30-day follow-up. Patients experienced less early pain (P Conclusion TEP inguinal hernia repair is associated with less early postoperative pain compared to the open glue mesh fixation technique. Trial registration NCT03566433 (http://www.clinicaltrials.gov).

Importance Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known. Objective To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography–confirmed uncomplicated acute appendicitis. Design, Setting, and Participants The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography–confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019. Interventions Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days. Main Outcomes and Measures The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference. Results Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was −3.6% ([1-sided 95% CI, −9.7% to ∞];P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin. Conclusion and Relevance Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics. Trial Registration ClinicalTrials.gov Identifier:NCT03236961; EudraCT Identifier:2015-003633-10

Objective 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. Methods Based on a database search, 72 of the 136 genes at the 13 obesity loci encoded multiple protein isoforms. Thus, alternative splicing of these genes in adipose tissue samples was analyzed from the Metabolic Syndrome in Men population-based study and from two weight loss intervention studies (surgical and very low calorie diet). Results Alternative splicing was confirmed in 11 genes with PCR capillary electrophoresis in human subcutaneous adipose tissue. Interestingly, differential splicing of TRA2B, BAG6, and MSH5 was observed between lean individuals with normoglycemia and overweight individuals with type 2 diabetes. Of these genes, we detected fat depot-dependent splicing of TRA2B and BAG6 and weight loss-induced regulation of MSH5 splicing in the intervention studies. Finally, body mass index was a major determinant of TRA2B, BAG6, and MSH5 splicing in the combined data. Conclusions This study provides evidence for alternative splicing in obesity loci, suggesting that alternative splicing at least in part mediates the obesity-associated risk in these loci.

BackgroundSportsman's hernia/athletic pubalgia is a recognized cause of chronic groin pain in athletes. Both open and laparoscopic surgical repairs have been described for treatment, but there are no comparative studies. The hypothesis here was that relief of pain would be achieved earlier in patients treated with open minimal suture repair than totally extraperitoneal repair.MethodsA randomized multicentre trial in four European countries was conducted to compare open minimal suture repair with totally extraperitoneal repair. The primary endpoint was complete relief of pain (visual analogue scale (VAS) score 20 or less on a scale from 0 to 100 mm) at 1 month. Secondary endpoints included complications, time to return to sporting activity, and number of patients returning to sport within 1 year.ResultsA total of 65 athletes (92 per cent men) with a median age of 29 years were enrolled (31 open repair, 34 totally extraperitoneal repair). By 4 weeks after surgery, median preoperative VAS scores had dropped from 70–80 to 10–20 in both groups (P < 0·001). Relief of pain (VAS score 20 or less) during sports activity 4 weeks after surgery was achieved in 14 of 31 patients after open repair and 24 of 34 after totally extraperitoneal repair (P = 0·047). Return to full sporting activity was achieved by 16 and 18 patients respectively after 1 month (P = 0·992), and by 25 versus 31 after 3 months (P = 0·408).ConclusionTotally extraperitoneal repair was less painful than open repair in the first month, but otherwise both procedures were similarly effective in treating chronic pain due to sportsman's hernia. Registration number: NCT02297711 ( http://www.clinical.trials.gov).

Based on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70–80%) or complicated (20–30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis. APPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients. Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin. To our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis. Clinicaltrials.gov , NCT03236961, retrospectively registered on the 2nd of August 2017.

Correction: Volume: 22 Issue: 5 Pages: 819-819 DOI: 10.1007/s10029-018-1788-y WOS:000446065400016 Chronic pain after inguinal hernioplasty is the foremost side-effect up to 10-30% of patients. Mesh fixation may influence on the incidence of chronic pain after open anterior mesh repairs. Some 625 patients who underwent open anterior mesh repairs were randomized to receive one of the three meshes and fixations: cyanoacrylate glue with low-weight polypropylene mesh (n = 216), non-absorbable sutures with partially absorbable mesh (n = 207) or self-gripping polyesther mesh (n = 202). Factors related to chronic pain (visual analogue scores; VAS ae 30, range 0-100) at 1 year postoperatively were analyzed using logistic regression method. A second analysis using telephone interview and patient records was performed 2 years after the index surgery. At index operation, all patient characteristics were similar in the three study groups. After 1 year, chronic inguinal pain was found in 52 patients and after 2 years in only 16 patients with no difference between the study groups. During 2 years' follow-up, three (0.48%) patients with recurrences and five (0.8%) patients with chronic pain were re-operated. Multivariate regression analysis indicated that only new recurrent hernias and high pain scores at day 7 were predictive factors for longstanding groin pain (p = 0.001). Type of mesh or fixation, gender, pre-operative VAS, age, body mass index or duration of operation did not predict chronic pain. Only the presence of recurrent hernia and early severe pain after index operation seemed to predict longstanding inguinal pain.

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.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.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.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.

Gallstone disease (GD) has been associated with low serum levels of plant sterols. We evaluated the impact of laparoscopic Roux-en-Y gastric bypass (LRYGB) and non-alcoholic fatty liver disease (NAFLD) on the association of GD with low levels of serum plant sterols. Two hundred forty-two consecutive morbidly obese patients were recruited to this prospective study. Histological analysis of liver biopsy to diagnose NAFLD was performed. Bile sample was taken during the LRYGB. Associations of GD with serum non-cholesterol sterol to cholesterol ratios, measured using gas liquid chromatography and with mRNA expression of genes participating in the cholesterol, bile, and fatty acid metabolism in the liver, were analyzed. Out of the 242 participants, 95 had GD. Lower weight (p = 0.002) and female sex (p = 0.0006) were associated with GD. Serum plant sterols, campesterol (p = 0.003), sitosterol (p = 0.002), and avenasterol (p = 0.015), were lower in patients with GD compared to those without GD. This association remained significant after adjustment for NAFLD, use of statin medication, and previous laparoscopic cholecystectomy (LCC). Levels of sitosterol (p = 0.001) and campesterol (p = 0.001) remained lower in obese individuals with GD also after obesity surgery. Liver mRNA expression of genes regulating cholesterol synthesis and bile metabolism was increased in individuals with GD. Serum plant sterols were lower in patients with GD independent of NAFLD, history of LCC, use of statin medication, and weight loss after LRYGB. Low serum plant sterols in patients with GD suggest potentially inherited alterations in sterol absorption and biliary transport in subjects susceptible for GD.

The incidence of acute appendicitis has declined in many countries. The aim of this study was to determine the trends in incidence of acute appendicitis (AA), appendectomies for AA, and nonspecific abdominal pain (NSAP) in Finland between 1987 and 2007.We carried out a national register study. Demographic features were investigated. Diagnoses and procedures were classified according to the World Health Organization International Classification of Diseases. Data were analyzed for each of all five University Hospital districts (UHD) of Finland.During the observation period of 21 years, 186,558 appendectomies were performed in Finland, of which 137,528 (74%) cases were reported as AA. The incidence of acute appendicitis declined 32%. The diagnostic accuracy improved from 73 to 82% and was higher in men. The accuracy rate among the male patients was stable throughout the two decades; among the female patients it rose from 63 to 75%. The incidence of appendicitis was highest in patients aged 15-24 years. The average incidence of NSAP was 34/10,000/year, and it was higher in older age groups. There was a large geographical disparity in the incidence of NSAP.The incidence of acute appendicitis as well as the incidence of appendectomies is declining in Finland. The incidence of the NSAP has also been declining but we did not find any correlations between the incidences of the acute appendicitis and NSAP. There were clear geographical differences in the incidence of NSAP but not in the incidence of AA.

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.Mesh fixation method may influence on the incidence of chronic pain after Lichtenstein hernioplasty.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.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.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.

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 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.

To assess the need for surgical treatment in patients with acute abdominal pain in a prospective randomized study.Initially 203 patients with acute abdominal pain were randomized to the routine abdominal computed tomography CT (rCT, n=118), or selective abdominal CT group (sCT, n=85) over a period of 16 months. Ninety-three of the randomized patients (45.8%) underwent the study design and were reached for follow-up at three months.Diagnostic accuracy improved significantly in the rCT group (p0.001). The surgeon's assessment of the need for surgery changed more often in the rCT group than in the sCT group (78.7% vs. 46.9%, p=0.002). The confidence to treat operatively increased significantly in the rCT vs. the sCT group (65.6% vs. 40.6%, p=0.028). The rCT was the only independent parameter for the change of the assessment of surgery.Routine CT allows for more confidence in decision making for the surgical treatment of patients with acute abdominal pain.

We 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.A 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.Lower 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.In 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.

The 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.To 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).Expression 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.INSR 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.

Data about the implementation of long-term follow-up of weight loss operation patients and their nutritional status has been lacking in Finland.We examined the postoperative complications and long-term outcome in respect of weight control, symptoms, nutritional status and medication of 173 patients having undergone gastric bypass. The data were collected from patient records and by questionnaires.Postoperative complications and weight loss were at the international level. The number of those using antidiabetic and antihypertensive drugs decreased.The results are in agreement with the international level, but follow-up treatment requires attention 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.