Operative Verfahren bei hohen kryptoglandulären Analfisteln: Systematische Übersicht und Metaanalyse

Purpose: Perianal fistulas, and specifically high perianal fistulas, remain a challenge for surgical treatment. Many techniques have been and are still being developed to improve the outcome after surgery. A systematic review and meta-analysis was performed for surgical treatment of high cryptoglandular perianal fistulas. Methods: Medline (Pubmed, Ovid), Embase and The Cochrane Library databases were searched for relevant randomized controlled trials on surgical treatments for high cryptoglandular perianal fistulas. Two independent reviewers selected articles for inclusion based on title, abstract and outcomes described. The main outcome measurement was the recurrence/healing rate. Secondary outcomes were continence status, quality of life and complications. Results: The number of randomized trials available was low. Fourteen studies could be included in the review. A meta-analysis could only be performed for the mucosal advancement flap versus the fistula plug, and did not show a result in favour of either technique in recurrence or complication rate. The mucosal advancement flap was the most investigated technique but did not show any advantage over any other technique. Other techniques identified in randomized studies were seton treatment, medicated seton treatment, fibrin glue, autologous stem cells, island flap anoplasty, rectal wall advancement flap, ligation of the intersphincteric fistula tract, sphincter reconstruction, sphincter-preserving seton and techniques combined with antibiotics. None of these techniques seemed superior to each other. Conclusions: The best surgical treatment for high cryptoglandular perianal fistulas could not be identified. More randomized controlled trials are needed to find the best treatment. The mucosal advancement flap is the most investigated technique available

Enhanced Membrane Pore Formation through High-Affinity Targeted Antimicrobial Peptides

Many cationic antimicrobial peptides (AMPs) target the unique lipid composition of the prokaryotic cell membrane. However, the micromolar activities common for these peptides are considered weak in comparison to nisin, which follows a targeted, pore-forming mode of action. Here we show that AMPs can be modified with a high-affinity targeting module, which enables membrane permeabilization at low concentration. Magainin 2 and a truncated peptide analog were conjugated to vancomycin using click chemistry, and could be directed towards specific membrane embedded receptors both in model membrane systems and whole cells. Compared with untargeted vesicles, a gain in permeabilization efficacy of two orders of magnitude was reached with large unilamellar vesicles that included lipid II, the target of vancomycin. The truncated vancomycin-peptide conjugate showed an increased activity against vancomycin resistant Enterococci, whereas the full-length conjugate was more active against a targeted eukaryotic cell model: lipid II containing erythrocytes. This study highlights that AMPs can be made more selective and more potent against biological membranes that contain structures that can be targeted

Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins

Peptidoglycan is an essential component of the bacterial cell envelope that surrounds the cytoplasmic membrane to protect the cell from osmotic lysis. Important antibiotics such as β-lactams and glycopeptides target peptidoglycan biosynthesis. Class A penicillin-binding proteins (PBPs) are bifunctional membrane-bound peptidoglycan synthases that polymerize glycan chains and connect adjacent stem peptides by transpeptidation. How these enzymes work in their physiological membrane environment is poorly understood. Here, we developed a novel Förster resonance energy transfer-based assay to follow in real time both reactions of class A PBPs reconstituted in liposomes or supported lipid bilayers and applied this assay with PBP1B homologues from Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii in the presence or absence of their cognate lipoprotein activator. Our assay will allow unravelling the mechanisms of peptidoglycan synthesis in a lipid-bilayer environment and can be further developed to be used for high-throughput screening for new antimicrobials

Transposition of the tendon of the M. tibialis posterior as an effective operative treatment of a drop foot

Objective. To evaluate the results of transposition of the tendon of the M. tibialis posterior in patients with a drop foot. Design. Descriptive, retrospective and follow-up investigation. Methods. Surgical treatment was carried out in 12 patients with a drop foot (9 women and 3 men, with an average age of 37 years) in the period 1986-1998. The aetiology of the drop foot was a traumatic or iatrogenic lesion of the peroneal nerve or sciatic nerve in 9 patients and in 3 patients spina bifida occulta, leprosy and a herniation of a lumbar disc respectively. None of the patients had important comorbidity. Treatment consisted of lengthening the Achilles tendon according to Huckstep, transposition of the tibial posterior tendon in two tails to the dorsomedial and dorsolateral side of the foot, and six weeks of immobilisation in plaster of Paris. Results. The postoperative period was without complications. The treatment improved the heel-toe steppage gait in all patients. None of the 10 patients who had used an orthosis preoperatively still used it at the time of the follow up. Fifty per cent of the patients acquired a dorsiflexion of the foot of more than 0°. The results were in accordance with those in the literature. Conclusion. Transposition of the tibial posterior tendon is a worthwhile alternative for those patients with a drop foot (and without important comorbidity) who cannot walk satisfactorily with an ankle-foot orthosis.</p

Transposition of the tendon of the M. tibialis posterior as an effective operative treatment of a drop foot

Objective. To evaluate the results of transposition of the tendon of the M. tibialis posterior in patients with a drop foot. Design. Descriptive, retrospective and follow-up investigation. Methods. Surgical treatment was carried out in 12 patients with a drop foot (9 women and 3 men, with an average age of 37 years) in the period 1986-1998. The aetiology of the drop foot was a traumatic or iatrogenic lesion of the peroneal nerve or sciatic nerve in 9 patients and in 3 patients spina bifida occulta, leprosy and a herniation of a lumbar disc respectively. None of the patients had important comorbidity. Treatment consisted of lengthening the Achilles tendon according to Huckstep, transposition of the tibial posterior tendon in two tails to the dorsomedial and dorsolateral side of the foot, and six weeks of immobilisation in plaster of Paris. Results. The postoperative period was without complications. The treatment improved the heel-toe steppage gait in all patients. None of the 10 patients who had used an orthosis preoperatively still used it at the time of the follow up. Fifty per cent of the patients acquired a dorsiflexion of the foot of more than 0°. The results were in accordance with those in the literature. Conclusion. Transposition of the tibial posterior tendon is a worthwhile alternative for those patients with a drop foot (and without important comorbidity) who cannot walk satisfactorily with an ankle-foot orthosis.</p

External validation and updating of prediction models for estimating the 1-year risk of low health-related quality of life in colorectal cancer survivors

Objectives Timely identification of colorectal cancer (CRC) survivors at risk of experiencing low health-related quality of life (HRQoL) in the near future is important for enabling appropriately tailored preventive actions. We previously developed and internally validated risk prediction models to estimate the 1-year risk of low HRQoL in long-term CRC survivors. In this article, we aim to externally validate and update these models in a population of short-term CRC survivors. Study Design and Setting In a pooled cohort of 1,596 CRC survivors, seven HRQoL domains (global QoL, cognitive/emotional/physical/role/social functioning, and fatigue) were measured prospectively at approximately 5 months postdiagnosis (baseline for prediction) and approximately 1 year later by a validated patient-reported outcome measure (European Organization for Research and Treatment of Cancer Quality of life Questionnaire–Core 30). For each HRQoL domain, 1-year scores were dichotomized into low vs. normal/high HRQoL. Performance of the previously developed multivariable logistic prediction models was evaluated (calibration and discrimination). Models were updated to create a more parsimonious predictor set for all HRQoL domains. Results Updated models showed good calibration and discrimination (AUC ≥0.75), containing a single set of 15 predictors, including nonmodifiable (age, sex, education, time since diagnosis, chemotherapy, radiotherapy, stoma, and comorbidities) and modifiable predictors (body mass index, physical activity, smoking, anxiety/depression, and baseline fatigue and HRQoL domain scores). Conclusion Externally validated and updated prediction models performed well for estimating the 1-year risk of low HRQoL in CRC survivors within 6 months postdiagnosis. The impact of implementing the models in oncology practice to improve HRQoL outcomes in CRC survivors needs to be evaluated