Randomized clinical trial of open suture repair versus totally extraperitoneal repair for treatment of sportsman's hernia.

BACKGROUND: Sportsman'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. METHODS: A 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. RESULTS: A 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). CONCLUSION: Totally 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).

Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial).

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03236961, retrospectively registered on the 2nd of August 2017.

Correction to: Factors predicting chronic pain after open inguinal hernia repair: a regression analysis of randomized trial comparing three different meshes with three fixation methods (FinnMesh Study).

In the original publication, co-authors affiliations were incorrect.

Factors predicting chronic pain after open inguinal hernia repair: a regression analysis of randomized trial comparing three different meshes with three fixation methods (FinnMesh Study).

BACKGROUND: 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. METHODS: 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 ≥ 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. RESULTS: 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. CONCLUSION: Only the presence of recurrent hernia and early severe pain after index operation seemed to predict longstanding inguinal pain.

Long-term outcome of patients with acute non-specific abdominal pain compared to acute appendicitis: prospective symptom audit after two decades.

BACKGROUND: Non-specific abdominal pain (NSAP) and acute appendicitis (AA) are the two most frequent diagnoses of acute abdomen in the emergency wards. The long-term morbidity, mortality and quality of life of the patients with NSAP compared to AA are unknown. METHODS: The study group consisted of 186 patients with acute NSAP compared to 147 patients with AA initially treated during 1985-1986. Medical history, social background, quality of life and abdominal symptoms were assessed with standardized questionnaires in both groups during 2006-2009. The patients who continued to have abdominal symptoms were invited to a check-up visit. RESULTS: During 1985-6, the NSAP group had more previous abdominal symptoms and operations than the AA group. Some 29% of patients with NSAP and 11% of patients with AA had still abdominal symptoms at long-term check-up (p < 0.0001). Chronic abdominal pain (38 vs 17) and peptic ulcer disease (18 vs 2) occurred more often in the NSAP group than in the controls, respectively (p = 0.001). After five years of follow-up, 11 patients in the NSAP group and 6 patients in the AA group had died (ns). During the twenty years of follow-up, mortality was higher (46/22, 25/15%) in the patients with NSAP than in controls (p = 0.013). Ischaemic heart disease was the leading cause of death in both groups (18 NSAP vs 5 AA, p = 0.017). The quality of life scores were comparable in both study groups. CONCLUSION: Over 70% of NSAP- and almost 90% of AA-patients were free of symptoms after 20 years of follow-up. Mortality was higher and various alimentary track diseases were more frequent in patients with NSAP than in AA.

Genetic risk score does not predict the outcome of obesity surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Long-term episomal maintenance of bovine papillomavirus type 1 plasmids is determined by attachment to host chromosomes, which Is mediated by the viral E2 protein and its binding sites.

Papillomavirus genomes are stably maintained as extrachromosomal nuclear plasmids in dividing host cells. To address the mechanisms responsible for stable maintenance of virus, we examined nuclear compartmentalization of plasmids containing the full-length upstream regulatory region (URR) from the bovine papillomavirus type 1 (BPV1) genome. We found that these plasmids are tightly associated with the nuclear chromatin both in the stable cell lines that maintain episomal copies of the plasmids and in transiently transfected cells expressing the viral E1 and E2 proteins. Further analysis of viral factors revealed that the E2 protein in trans and its multiple binding sites in cis are both necessary and sufficient for the chromatin attachment of the plasmids. On the other hand, the BPV1 URR-dependent plasmid replication and chromatin attachment processes are clearly independent of each other. The ability of the plasmids to stably maintain episomes correlates clearly with their chromatin association function. These data suggest that viral E2 protein-mediated attachment of BPV1 genomes to the host cell chromatin could provide a mechanism for the coupling of viral genome multiplication and partitioning to the host cell cycle during viral latent infection.

p53 protein is a suppressor of papillomavirus DNA amplificational replication.

p53 protein was able to block human and bovine papillomavirus DNA amplificational replication while not interfering with Epstein-Barr virus oriP once-per-cell cycle replication. Oligomerization, intact DNA-binding, replication protein A-binding, and proline-rich domains of the p53 protein were essential for efficient inhibition, while the N-terminal transcriptional activation and C-terminal regulatory domains were dispensable for the suppressor activity of the p53 protein. The inhibition of replication was caused neither by the downregulation of expression of the E1 and E2 proteins nor by cell cycle block or apoptosis. Our data suggest that the intrinsic activity of p53 to suppress amplificational replication of the papillomavirus origin may have an important role in the virus life cycle and in virus-cell interactions.