Julian C. Harnoss

Antibiotics Versus Surgical Therapy for Uncomplicated Appendicitis: Systematic Review and Meta-analysis of Controlled Trials (PROSPERO 2015: CRD42015016882).

Objective: The aim was to investigate available evidence regarding effectiveness and safety of surgical versus conservative treatment of acute appendicitis. Summary of Background Data: There is ongoing debate on the merits of surgical and conservative treatment for acute appendicitis. Methods: A systematic literature search (Cochrane Library, Medline, Embase) and hand search of retrieved reference lists up to January 2016 was conducted to identify randomized and nonrandomized studies. After critical appraisal, data were analyzed using a random-effects model in a Mantel-Haenszel test or inverse variance to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results: Four trials and four cohort studies (2551 patients) were included. We found that 26.5% of patients in the conservative group needed appendectomy within 1 year, resulting in treatment effectiveness of 72.6%, significantly lower than the 99.4% in the surgical group, (RR 0.75; 95% CI 0.7–0.79; P = 0.00001; I2 = 62%). Overall postoperative complications were comparable (RR 0.95; 95% CI 0.35–2.58; P = 0.91; I2 = 0%), whereas the rate of adverse events (RR 3.18; 95% CI 1.63–6.21; P = 0.0007; I2 = 1%) and the incidence of complicated appendicitis (RR 2.52; 95% CI 1.17–5.43; P = 0.02; I2 = 0%) were significantly higher in the antibiotic treatment group. Randomized trials showed significantly longer hospital stay in the antibiotic treatment group (RR 0.3 days; 95% CI 0.07–0.53; P = 0.009; I2 = 49%). Conclusions: Although antibiotics may prevent some patients from appendectomies, surgery represents the definitive, one-time only treatment with a well-known risk profile, whereas the long-term impact of antibiotic treatment on patient quality of life and health care costs is unknown. This systematic review and meta-analysis helps physicians and patients in choosing between treatment options depending on whether they are risk averse or risk takers.

Therapeutic inhibition of prolyl hydroxylase domain-containing enzymes in surgery: putative applications and challenges

Oxygen is essential for metazoans to generate energy. Upon oxygen deprivation adaptive and protective pathways are induced, mediated by hypoxia-inducible factors (HIFs) and prolyl hydroxylase domain-containing enzymes (PHDs). Both play a pivotal role in various conditions associated with prolonged ischemia and inflammation, and are promising targets for therapeutic intervention. This review focuses on aspects of therapeutic PHD modulation in surgically relevant disease conditions such as hepatic and intestinal disorders, wound healing, innate immune responses, and tumorigenesis, and discusses the therapeutic potential and challenges of PHD inhibition in surgical patients.

Placebo-Controlled Trials in Surgery: A Systematic Review and Meta-Analysis

AbstractThis systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. “Surgical procedure” was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92–2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.

Antibiotics Versus Appendicectomy for the Treatment of Uncomplicated Acute Appendicitis: An Updated Meta-Analysis of Randomised Controlled Trials by Rollins et al.

Dear Editors, We read the article by Rollins et al. [1] with great interest. This updated systematic review and meta-analysis is showing an intensive reflection of current debates and thus deserves a comment on results and its final conclusion that antibiotics should be prescribed once a diagnosis of acute appendicitis is made or considered and that the primary treatment of acute uncomplicated appendicitis should be antibiotics. In our opinion [2], this conclusion is hastily and not supported by current available data. The main general critics are that we do not have any data about peri-interventional quality of life of our patients and no follow-up of longer than one year after initial therapy. Moreover, adverse events of the antibiotic therapy were insufficiently reported by most of trials. Besides the fact that the choice, application form, dosage and treatment duration of antibiotics are unclear, we should be aware of the risk of supporting antibiotic resistances and danger to treat malignancies with antibiotics if not performing a CT scan which will have its own drawbacks. Furthermore, none of the trials investigating antibiotics as primary therapy considered repeating hospital stays as burden of this kind of treatment. In accordance with our results, antibiotics may prevent 62.6–72.6% of patients from appendectomies [1, 2]. Nevertheless, going one step further, thorough and proper metaand subgroup analyses revealed that treatment failure of antibiotics occurred in 46.4% up to 1 year after the initial hospital stay and the risk of complicated appendicitis was significantly increased by twofold [2]. In conclusion, surgery represents a final treatment with a clear risk profile and important factors on antibiotic therapy are yet uninvestigated (e.g. quality of life). Therefore, we plead for further RCTs and a transparent discussion of treatment options, interdisciplinary and patient-oriented in cases with suspected acute, uncomplicated appendicitis rather than a premature change of paradigm based on currently insufficient data.

Prospective mixed-methods study of patients undergoing relaparotomy (ReLap study; DRKS00013001)

Highlights • Patients undergoing relaparotomies are underrepresented in clinical trials.• The study has three steps: health care research, translational research, and RCT.• The clinical course will be followed prospectively.• Main outcomes are postoperative complications, incisional hernias and adhesions.• The ReLap study will gain evidence for best care in relaparotomies.

Comparison of chlorhexidine–isopropanol with isopropanol skin antisepsis for prevention of surgical‐site infection after abdominal surgery

Prevention of surgical‐site infection (SSI) has received increasing attention. Clinical trials have focused on the role of skin antisepsis in preventing SSI. The benefit of combining antiseptic chlorhexidine with alcohol has not been compared with alcohol‐based skin preparation alone in a prospective controlled clinical trial.