Respiratory infections caused by multidrug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality among critically ill hospitalized patients. Bacteriophages (phages) eliminate pathogens with high host specificity and efficacy. However, the lack of appropriate preclinical experimental models hampers the progress of clinical development of phages as therapeutic agents. Therefore, we tested the efficacy of a purified lytic phage, vB_AbaM_Acibel004, against multidrug-resistant A. baumannii clinical isolate RUH 2037 infection in immunocompetent mice and a human lung tissue model. Sham- and A. baumannii-infected mice received a single-dose of phage or buffer via intratracheal aerosolization. Group-specific differences in bacterial burden, immune and clinical responses were compared. Phage-treated mice not only recovered faster from infection-associated hypothermia but also had lower pulmonary bacterial burden, lower lung permeability, and cytokine release. Histopathological examination revealed less inflammation with unaffected inflammatory cellular recruitment. No phage-specific adverse events were noted. Additionally, the bactericidal effect of the purified phage on A. baumannii was confirmed after single-dose treatment in an ex vivo human lung infection model. Taken together, our data suggest that the investigated phage has significant potential to treat multidrug-resistant A. baumannii infections and further support the development of appropriate methods for preclinical evaluation of antibacterial efficacy of phages.

Incisional hernia is a frequent complication in abdominal surgery. This article describes the development of a prospective randomized clinical trial designed to determine whether watchful waiting is an acceptable alternative to surgical repair for patients with oligosymptomatic incisional hernia. This clinical multicenter trial has been designed to compare watchful waiting and surgical repair for patients with oligosymptomatic incisional hernia. Participants are randomized to watchful waiting or surgery and followed up for two years. The primary efficacy endpoint is pain/discomfort during normal activities as a result of the hernia or hernia repair two years after enrolment, as measured by the hernia-specific Surgical Pain Scales (SPS). The target sample size of six hundred thirty-six patients was calculated to detect non-inferiority of the experimental intervention (watchful waiting) in the primary endpoint. Sixteen surgical centers will take part in the study and have submitted their declaration of commitment giving the estimated number of participating patients per year. A three-person data safety monitoring board will meet annually to monitor and supervise the trial. To date, we could find no published data on the natural course of incisional hernias. To our knowledge, watchful waiting has never been compared to standard surgical repair as a treatment option for incisional hernias. A trial to compare the outcome of the two approaches in patients with oligosymptomatic incisional hernias is urgently needed to provide data that can facilitate the choice between treatment options. If watchful waiting was equal to surgical repair, the high costs of surgical repair could be saved. The design for such a trial is described here. This multicenter trial will be funded by the German Research Foundation (DFG). The ethics committee of the Charité has approved the study protocol. Approval has been obtained from ten study sites at time of this submission. The electronic Case Report Forms have been created. The first patient was to be randomized November 14^th, 2011. An initiation meeting took place in Berlin January 9^th, 2012. ClinicalTrials.gov: NCT01349400

Das Vorhandensein von Luft zwischen Pleura visceralis und Pleura parietalis mit konsekutivem Zurückweichen der Lunge von der Brustwand wird als Pneumothorax bezeichnet. Unterschieden wird nach der Genese des Pneumothorax in Spontanpneumothorax und traumatisch bedingten Pneumothorax. Der Spontanpneumothorax wird in Abhängigkeit von einer angeborenen oder erworbenen Lungenerkrankung unterteilt in einen primären Spontanpneumothorax (PSP) ohne zugrunde liegende Lungenerkrankung und in einen sekundären Spontanpneumothorax (SSP), dem eine bekannte Lungengerüsterkrankung zugrunde liegt. Ein traumatisch bedingter Pneumothorax wird hinsichtlich seiner Entstehung durch ein penetrierendes oder stumpfes Thoraxtrauma klassifiziert. Als spezielle Form des traumatisch bedingten Pneumothorax ist der iatrogene Pneumothorax zu werten, der als Folge einer ärztlichen Intervention zu diagnostischen und therapeutischen Zwecken auftritt. Klinisch kann ein Pneumothorax vom asymptomatischen Bild bis hin zur akut lebensbedrohlichen Situation reichen. Die erforderlichen Erstmaßnahmen sind primär vom klinischen Zustand des Patienten abhängig. Sie reichen von sofortiger Entlastung des Pneumothorax, z. B. durch Einlage einer Thoraxdrainage, bis hin zu Abwarten und Überwachung. Die Einlage einer Thoraxdrainage gilt nach wie vor als Therapiestandard, jedoch stellen auch andere Behandlungsmaßnahmen, insbesondere bei kleinen Spontanpneumothoraces, wie die Aspiration von Luft über eine Nadel oder kleinere Katheter Therapieoptionen dar. Kurzfristiges Ziel ist es, eine Wiederausdehnung der Lunge zu erreichen sowie mögliche Symptome wie Dyspnoe und thorakale Schmerzen zu lindern. Langfristiges Ziel ist es, ein mögliches Rezidiv zu verhindern. Weder für das Erreichen der kurzfristigen Ziele noch für die langfristige Rezidivfreiheit gibt es derzeit einheitliche Behandlungsalgorithmen oder standardisierte Therapieprinzipien. The presence of air between the visceral pleura and the parietal pleura with consecutive retraction of the lung from the chest wall is called pneumothorax. Regarding the genesis of the pneumothorax, a distinction is drawn between spontaneous and traumatic pneumothorax. The spontaneous pneumothorax is, depending on whether a congenital or an acquired pulmonary disease can be found, grouped into a primary spontaneous pneumothorax (PSP) without underlying lung disease and a secondary spontaneous pneumothorax (SSP) with the presence of a known lung disease. The traumatic pneumothorax is classified, depending on the cause, into penetrating and non-penetrating (blunt) traumatic events. A special form of the traumatic pneumothorax is the iatrogenic pneumothorax occurring as a result of diagnostic and/or therapeutic interventions. Clinically, a pneumothorax can range from an asymptomatic to an acute life-threatening situation. The required initial measures depend primarily on the patientʼs clinical condition. They vary from immediate insertion of a chest tube to wait and see with monitoring. The insertion of a chest tube is still the accepted therapeutic standard, but other procedures like aspiration of air through a needle or small catheter, particularly for small spontaneous pneumothoraces, represent alternative therapy options as well. The short-term goal is to treat possibly existing dyspnea and pain; in the long run a recurrence of the pneumothorax should be prevented. Until now, no uniform treatment algorithms or standardised therapy principles exist to achieve the therapeutic intentions of lung expansion and freedom from pain and late relapse. ^* Beide Autoren haben zu gleichen Teilen zur Erstellung des Manuskripts beigetragen.

Background: Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus^® such a suture has now been made available with triclosan antibacterial coating. Methods/Design: The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n = 750 is sufficient to ensure alpha = 5% and power = 80%, an interim analysis will be carried out after data of 375 patients are available. Discussion: The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity. Trial Registration: The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390).

For the surgical treatment of recurrent primary spontaneous pneumothoraces (rPSP) different operative therapies are applied to achieve permanent freedom from recurrence. This multicenter clinical trial evaluates the long-term results of two commonly applied surgical techniques for the treatment of rPSP. Based on the inclusion and exclusion criteria, and after obtaining the patients’ informed consent, participants are randomized into the two surgical treatment arms: pulmonary wedge resection plus parietal pleurectomy (WRPP) or parietal pleurectomy alone (PP). Consecutively, all study participants will be followed up for two years to evaluate the surgical long-term effect. The primary efficacy endpoint is the recurrence rate of pneumothorax within 24 months after surgery. The calculated sample size is 360 patients (n = 180 per treatment arm) to prove superiority of one of the two treatments. So far, 22 surgical sites have submitted their declaration of commitment, giving the estimated number of participating patients. A prospective randomized clinical trial has been started to compare two established surgical therapies to evaluate the long-term results regarding recurrence rates. Furthermore, cost of treatment, and influence on the perioperative morbidity and mortality as well as on quality of life are analyzed. If the study reveals equivalence for both surgical techniques, unnecessary pulmonary resections could be avoided. ClinicalTrials gov: NCT01855464 , 06.05 2013.