Host-pathogen interaction during mechanical ventilation: systemic or compartmentalized response?

Patients admitted to the intensive care unit (ICU) often require invasive mechanical ventilation. Ventilator-associated lower respiratory tract infections (VA-LRTI), either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP), are the most common complication among this patient cohort. VAT and VAP are currently diagnosed and treated as separate entities, viewed as binary disease elements despite an inherent subjectivity in distinguishing them clinically. This paper describes a new approach to pulmonary infections in critically ill patients. Our conjecture is that the host-pathogen interaction during mechanical ventilation determines a local compartmentalized or systemic de-compartmentalized response, based on host immunity and inflammation, and the pathogenic potential of the infecting organism. This compartmentalized or de-compartmentalized response establishes disease severity along a continuum of colonization, VAT or VAP. This change in approach is underpinned by the dissemination hypothesis, which acknowledges the role of immune and inflammatory systems in determining host response to pathogenic organisms in the lower respiratory tract. Those with intact immune and inflammatory pathways may limit infection to a compartmentalized VAT, while immunosuppressed mechanically ventilated patients are at greater risk of a de-compartmentalized VAP. Taking this model from the realm of theory to the bedside will require a greater understanding of inflammatory and immune pathways, and the development of novel disease-specific biomarkers and diagnostic techniques. Advances will lead to early initiation of optimal bespoke antimicrobial therapy, where the intensity and duration of therapy are tailored to clinical, immune and biomarker response. This approach will benefit towards a personalized treatment.

Immunological mechanisms of tolerance: Central, peripheral and the role of T and B cells.

T and B cells are key components of the adaptive immune system. Through their immune properties and their interactions with other immune cells and cytokines around them, they build a complex network to achieve immune tolerance and maintain homeostasis of the body. This is achieved through mechanisms of central and peripheral tolerance, both of which are associated with advantages and disadvantages. For this reason, the immune system is tightly regulated and their dysregulation can result in the subsequent initiation of various diseases. In this review, we will summarize the roles played by T cells and B cells within immune tolerance with specific examples in the context of different diseases that include allergic disease. In addition, we will also provide an overview on their suitability as biomarkers of allergen-specific immunotherapy.

Visual Search in 3D: Effects of Monoscopic and Stereoscopic Cues to Depth on the Validity of Feature Integration Theory and Perceptual Load Theory.

Previous research has successfully used feature integration theory to operationalise the predictions of Perceptual Load Theory, while simultaneously testing the predictions of both models. Building on this work, we test the extent to which these models hold up in a 3D world. In two experiments, participants responded to a target stimulus within an array of shapes whose apparent depth was manipulated using a combination of monoscopic and stereoscopic cues. The search task was designed to test the predictions of (a) feature integration theory, as the target was identified by a single feature or a conjunction of features and embedded in search arrays of varying size, and (b) perceptual load theory, as the task included congruent and incongruent distractors presented alongside search tasks imposing high or low perceptual load. Findings from both experiments upheld the predictions of feature integration theory, regardless of 2D/3D condition. Longer search times in conditions with a combination of monoscopic and stereoscopic depth cues suggests that binding features into three-dimensional objects requires greater attentional effort. This additional effort should have implications for perceptual load theory, yet our findings did not uphold its predictions; the effect of incongruent distractors did not differ between conjunction search trials (conceptualised as high perceptual load) and feature search trials (low perceptual load). Individual differences in susceptibility to the effects of perceptual load were evident and likely explain the absence of load effects. Overall, our findings suggest that feature integration theory may be useful for predicting attentional performance in a 3D world.

Systematic review on the first line treatment of amphotericin B in critically ill adults with candidemia or invasive candidiasis.

INTRODUCTION: Invasive candidiasis is the most common fungal infection affecting critically ill adults. International guidelines provide differing recommendations for first-line antifungal therapy, with echinocandins considered first-line in the majority. Amphotericin B has broad activity and low minimum inhibitory concentration resistance patterns across most Candida species and guidance away from its use should be supported by the available evidence. Areas Covered: A systematic literature review was conducted from August to September 2017 to determine whether treatment with echinocandins or other available drugs, namely voriconazole, confers a therapeutic or survival benefit over amphotericin B in critically ill adults with invasive candidiasis. Inclusion criteria were: (1) studies describing critically ill adults with invasive candidiasis, (2) studies describing therapeutic benefit or survival as an outcome, and (3) studies comparing amphotericin B, deoxycholate or lipid preparations, with any newer antifungal agent. Eight studies were included in the final review, incorporating 2352 unique patients. No difference in treatment efficacy or mortality outcomes in critically ill patients with invasive candidiasis receiving an amphotericin B formulation compared with those receiving an echinocandin or voriconazole was shown. Expert Commentary: We conclude that in the existing literature, there is no evidence that choice between echinocandins, voriconazole, or amphotericin B formulations as first-line therapy for critically ill adults with invasive candidiasis is associated with a therapeutic or survival benefit. Clinicians must therefore consider other factors in the selection of first-line therapy.

How Can We Distinguish Ventilator-Associated Tracheobronchitis from Pneumonia?

Ventilator-associated tracheobronchitis (VAT) might represent an intermediate process between lower respiratory tract colonization and ventilator-associated pneumonia (VAP), or even a less severe spectrum of VAP. There is an urgent need for new concepts in the arena of ventilator-associated lower respiratory tract infections. Ideally, the gold standard of care is based on prevention rather than treatment of respiratory infection. However, despite numerous and sometimes imaginative efforts to validate the benefit of these measures, most clinicians now accept that currently available measures have failed to eradicate VAP. Stopping the progression from VAT to VAP could improve patient outcomes.

Day-case laparoscopic cholecystectomy: analysis of the factors allowing early discharge.

Despite a number of studies have already demonstrated that majority of patients can be safely discharged early after laparoscopic cholecystectomy, this approach did not gain widespread diffusion yet. The present study was set up to assess safety and feasibility of 24 h or same-day discharge after laparoscopic cholecystectomy and to identify the prognostic factors. Perioperative variables of 229 patients undergoing cholecystectomy have been analyzed. Primary endpoints were: postoperative length of stay, rate of patients discharged within 24 h, and rate of those discharged on the same day. Secondary endpoints were rate of 30-day readmission and rate of 30-day postoperative complications. Two-hundred twenty-three cases have been started by laparoscopy. Conversion rate was 3.1%. Overall mean postoperative stay was 1.8 ± 3.5 days (median 1 day). Seventy-eight percent of patients have been discharged within 24 h, and 22.3% have been discharged on the same day. Postoperative morbidity was 2.2%. Readmission rate was 3.9%. At univariate analysis, factors related to early discharge were age (more or less than 65), diagnosis (simple symptomatic gallstones vs complicated gallstones), ASA score, timing of operation (elective vs emergency), history of CBD stones, laparoscopic operation, and use of drain. No single factor was significantly related to readmission rate, but the use of drains in laparoscopic cases. At multivariate analysis, only elective operation, simple symptomatic gallstones, no history of CBD stones, laparoscopic approach, and no abdominal drain resulted independently associated with discharge within 24 h from the operation. The predictive models are all fit and significant. Early postoperative discharge within 24 h should be considered in all patients with simple symptomatic gallstones who had laparoscopic cholecystectomy. Same-day discharge should be considered if no drain was left at the end of the operation.

Major Pelvic Bleeding Following a Stapled Transanal Rectal Resection: Use of Laparoscopy as a Diagnostic Tool.

Stapled transanal rectal resection (STARR) and stapled hemorrhoidopexy (SH) are well-established techniques for treating rectal prolapse and obstructed defecation syndrome (ODS). Occasionally, they can be associated with severe complications. We describe the case of a 59-year-old woman who underwent STARR for ODS and developed a postoperative pelvic hemorrhage. A computed tomography (CT) scan revealed a vast pelvic, retroperitoneal hematoma and free gas in the abdomen. Laparoscopy ruled out any bowel lesions, but identified a hematoma of the pelvis. Flexible sigmoidoscopy showed a small leakage of the rectal suture. The patient was treated conservatively and recovered completely. Surgeons performing STARR and SH must be aware of the risk of this rare, but severe, complication. If the patient is not progressing after a STARR or SH, a CT scan can be indicated to rule out intra-abdominal and pelvic hemorrhage. Laparoscopy is a diagnostic tool and should be associated with intraluminal exploration with flexible sigmoidoscopy.

Early Discharge After Colorectal Resection: The Positive Impact of an Enhanced Recovery Program on a Rural Colorectal Surgery Service.

BACKGROUND: Enhanced recovery (ER) programs are policies and protocols meant to improve postoperative recovery after surgery. As a consequence of a smoother recovery, patients can be discharged early. This paper describes the impact of an ER program in colorectal surgery in a rural hospital. MATERIALS AND METHODS: In total, 132 patients had colorectal resection within the ER program. Data were collected prospectively. The ER pathway affects perioperative management in the following ways in order to: (1) improve patient's general condition before surgery, (2) minimize intraoperative surgical trauma by using a laparoscopic approach in all cases, and (3) facilitation of a quicker postoperative return of physiological function. RESULTS: Most (86.4%) of the patients have been operated as elective cases and for a cancer (73.5%). Laparoscopic resection was performed in 63.6% of patients, with a conversion rate of 10.6%. Total morbidity was 18.2%, leak rate was 1.5%, and 90-day mortality rate was 3%. Overall median postoperative stay was 6.5 days. Total length of in-hospital stay was lower in laparoscopic resections (5.5 d), elective cases (6 d), and in younger patients (6 d). Age and laparoscopic access were independent prognostic factors significantly associated with early discharge in elective patients. Overall readmission rate was 9.1% and this was not affected by any preoperative or intraoperative factor within those in this study. CONCLUSIONS: The ER program positively impacted the outcome of colorectal resections also in our rural setting. Discharging patients expeditiously did not affect postoperative morbidity or readmission rate.

Force-velocity relationship and stretch-shortening cycle function in sprint and endurance athletes.

This study examined the torque-velocity and power-velocity relationships of quadriceps muscle function, stretch shortening cycle function, and leg-spring stiffness in sprint and endurance athletes. Isokinetic maximal knee extension torque was obtained from 7 sprinters and 7 endurance athletes using a Con-trex isokinetic dynamometer. Torque and power measures were corrected for lean-thigh cross-sectional area and lean-thigh volume, respectively. Stretch-shortening cycle function and muscle stiffness measurements were obtained while subjects performed single-legged squat, countermovement, and drop-rebound jumps on an inclined sledge and force-plate apparatus. The results indicated that sprinters generated, on average, 0.15 +/- 0.05 N.m.cm(-2) more torque across all velocities compared with endurance athletes. Significant differences were also found in the power-velocity relationships between the 2 groups. The sprinters performed significantly better than the endurance athletes on all jumps, but there were no differences in prestretch augmentation between the groups. The average vertical leg stiffness during drop jumps was significantly higher for sprinters (5.86 N.m(-1)) compared with endurance runners (3.38 N.m(-1)). The findings reinforce the need for power training to be carried out at fast contraction speeds but also show that SSC function remains important in endurance running.