PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.

[Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial Pneumonia - Update 2017 - S3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and the Society for Virology]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie ­ Update 2017.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.

History of neurosurgery at Howard University: the nation's only historically black academic institution that practices neurological surgery.

Howard University Hospital has been a pillar for healthcare delivery in the Black community, an underserved sector of Washington, DC, since its founding in 1862. Neurological surgery, one of the many areas of service provided, was established by trailblazer Dr. Clarence Greene Sr., who was appointed the division's first chief in 1949. Because of the color of his skin, Dr. Greene had to complete his neurosurgical training at the Montreal Neurological Institute, as he was refused the opportunity to train in the United States. He went on to become the first African American to be board certified in neurological surgery in 1953. Drs. Jesse Barber, Gary Dennis, and Damirez Fossett, the subsequent division chiefs, have all continued Dr. Greene's legacy of providing academic enrichment and subserving a disparate population. Many patients who may not have received treatment otherwise have been able to receive exemplary neurosurgical care from them. Under their tutelage, numerous African American medical students have gone on to train in neurological surgery. Future directions include developing a residency program, collaborating with other neurosurgery programs in continental Africa and the Caribbean, and establishing a fellowship for training international students.

Immunomodulatory roles of PARPs: Shaping the tumor microenvironment, one ADP-ribose at a time.

PARPs encompass a small yet pervasive group of 17 enzymes that catalyze a post-translational modification known as ADP-ribosylation. PARP1, the founding member, has received considerable focus; however, in recent years, the spotlight has shifted to other members within the PARP family. In this opinion piece, we first discuss surprising findings that some FDA-approved PARP1 inhibitors activate innate immune signaling in cancer cells that harbor mutations in the DNA repair pathway. We then discuss hot-off-the-press genetic and pharmacological studies that reveal roles for PARP7, PARP11, and PARP14 in immune signaling in both tumor cells and tumor-associated immune cells. We conclude with thoughts on tuning PARP1-inhibitor-mediated innate immune activation and explore the unrealized potential for small molecule modulators of other PARP family members as next-generation immuno-oncology drugs.

Utility of prolonged prophylactic systemic antibiotics for wound drains in posterior spine surgery: a systematic review and meta-analysis.

OBJECTIVE: Closed suction drains, often used after posterior spinal surgery, pose a potential risk of infection. To combat this risk, many surgeons opt for a prolonged prophylactic antibiotic regimen. Since 2015, several studies have shown that prolonged prophylactic systemic antibiotics (PPSA) for drains provides no additional benefit in reducing surgical site infection (SSI) rates. However, most of these studies lacked sufficient power to make reliable conclusions. To date, there has been no meta-analysis conducted to further investigate this issue. The aim of this study was to investigate whether a regimen of PPSA reduces the incidence of deep SSIs in adult patients with closed suction drains following posterior spinal surgeries. METHODS: The protocol of the current systematic review was registered with PROSPERO. A systematic review of the literature in PubMed (Medline), Europe PMC, Embase, and Cochrane Review databases was conducted for all relevant literature with the keywords "spine," "antibiotics," "surgical site infection," "prophylaxis," and "drain." Retrospective and prospective studies investigating the effectiveness of PPSA in patients 18 years or older who underwent posterior cervical or thoracolumbar surgery and had postoperative wound drains were included. The primary outcome was the odds ratio for deep SSI based on the intervention (PPSA vs non-PPSA). The secondary outcomes were the rates of superficial and overall SSIs. RESULTS: From a total of 2558 titles identified from the search, 7 studies were chosen for final analysis. Three were randomized controlled trials (RCTs), and 4 were retrospective reviews. A total of 2446 patients were analyzed; 1149 received a PPSA regimen and 1297 received a non-PPSA regimen. Deep SSIs occurred in 45 patients (3.9%) and 46 patients (3.5%) in the PPSA and non-PPSA groups, respectively. The odds ratio for deep SSIs in the PPSA group compared with the non-PPSA group was 1.10 (95% CI 0.69-1.74), which was not statistically significant. Additionally, there were no differences in the rates of superficial and overall SSIs. There was a trend toward increased infections with multidrug-resistant bacteria (Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus) in the PPSA group; however, it was not possible to perform a durable statistical analysis because of the small number of reported organisms in the selected publications. CONCLUSIONS: This meta-analysis demonstrates that there is no reduction in rate of deep, superficial, and overall SSIs with prolonged prophylactic antibiotics after posterior spinal surgery involving the use of closed suction drains.

[Coincidence of traumatic tracheal rupture accompanied by ARDS. Illustrated by the example of a 17-year-old patient with multiple injuries]. / Koinzidenz der traumatischen Trachealruptur mit begleitendem ARDS. Beispiel anhand eines 17-jährigen polytraumatisierten Patienten.

Treatment and diagnosis of a traumatic tracheal rupture is a challenge. Due to the rarity of such injuries and the subtle and delayed clinical presentation it is difficult to diagnose. We present for the first time the successful management of a 17-year-old multiply injured patient with coincidental tracheal rupture and ARDS (acute respiratory distress syndrome) after a fall. Besides the case report and pathogenesis the essential diagnostic and therapeutic measures are mentioned and discussed. The circumstances surrounding the accident have to be balanced with the severity of the trauma to also exclude rare injuries with certainty. Finally level 1 trauma centers specialized in ARDS provide the best clinical setting for successful treatment of these life-threatening injuries.

[Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. S-3 Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.

Myocardial infarction (MI) triggers an inflammatory response that transitions from pro-inflammatory to reparative over time. Restoring sympathetic nerves in the heart after MI prevents arrhythmias. This study investigated if reinnervation altered the immune response after MI. This study used quantitative multiplex immunohistochemistry to identify the immune cells present in the heart 2 weeks after ischemia-reperfusion. Two therapeutics stimulated reinnervation, preventing arrhythmias and shifting the immune response from inflammatory to reparative, with fewer pro-inflammatory macrophages and more regulatory T cells and reparative macrophages. Treatments did not alter macrophage phenotype in vitro, which suggested reinnervation contributed to the altered immune response.

Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia.

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Central area for induction of anesthesia and job satisfaction.

A central area for induction of anesthesia (CAIA) is supposed to optimize processes of preoperative patient preparation for anesthesia. The purpose of this study was to assess whether the separation of the anesthesia process into anesthesia induction and anesthesia maintenance is associated with residents' job satisfaction. The central area for induction of anesthesia model (CAIA model) was prospectively compared to the conventional model of anesthesia being induced, maintained and ended by the same anesthetist. Quality of senior staff supervision for each day as well as workday satisfaction was additionally graded by a Likert-scale. More than 80% of residents considered their workday as satisfying or very satisfying, regardless of the model applied. Furthermore, work day satisfaction was significantly associated with the quality of supervision provided by the teaching staff. It was concluded that time and attention provided by the teaching staff rather than the anesthesia organisational model were the major determinants of workday satisfaction.

Evaluation of recombinant human SP-D in the rat premature lung model.

BACKGROUND: The lungs of premature and term babies are structurally different from the adult lungs. Preterm lungs are underdeveloped, non-compliant in terms of breathing, often need mechanical ventilation and these patients commonly develop syndromes as a consequence of their prematurity, such as bronchopulmonary dysplasia (BPD). Surfactant protein SP-D could be a therapy for BPD. However, there is a need for an animal model that resembles the structural characteristics of premature lungs to test SP-D and future molecules that will target the newborn population. The aim of this study was to develop and validate a pre-clinical model of early alveolarization and structurally premature lungs in 10-day-old rats, and establish the dose safety and distribution of rhSP-D administered intratracheally to premature lungs. METHODS: Ten-day-old Sprague Dawley rats were selected to develop the lung model. SP-D was administered intratracheally. Bronchoalveolar lavage fluid and lungs were collected to evaluate inflammation and SP-D distribution. RESULTS: The 10-day-old rat pup demonstrates early alveolarization features of premature lung development and it tolerates daily intratracheal injections for up to 14 days. The intratracheal administration of rhSP-D, at a dose of 8 mg/kg, does not induce an inflammatory response or histological signs of toxicity in the premature lung, even with a daily administration for 14 days. The pharmacokinetic distribution of rhSP-D in premature lungs has a half-life of ∼9 h, and the incorporation into blood is minimal. CONCLUSIONS: 10-day-old rats are a good pre-clinical animal model of premature lungs, and rhSP-D can be intratracheally administered at doses up to 8 mg/kg without expecting adverse reactions.

B.2.16 is a non-lethal modifier of the Dark82 mosaic eye phenotype in Drosophila melanogaster.

Genetic screens have been used to identify genes involved in the regulation of different biological processes. We identified growth mutants in a Flp/FRT screen using the Drosophila melanogaster eye to identify conditional regulators of cell growth and cell division. One mutant identified from this screen, B.2.16, was mapped and characterized by researchers in undergraduate genetics labs as part of the Fly-CURE. We find that B.2.16 is a non-lethal genetic modifier of the Dark82 mosaic eye phenotype.

Ventilator-associated pneumonia in trauma patients is associated with lower mortality: results from EU-VAP study.

BACKGROUND: Differences in trauma patients developing ventilator-associated pneumonia (VAP) are described regarding etiology and risk factors associated. We aim to describe the differences in outcomes in trauma and nontrauma patients with VAP. METHODS: A prospective, observational study conducted in 27 intensive care units from nine European countries. We included patients requiring invasive mechanical ventilation for >48 hours who developed VAP. Logistic regression model was used to assess the factors independently associated with mortality in trauma patients with VAP. RESULTS: A total of 2,436 patients were evaluated; 465 developed VAP and of these 128 (27.5%) were trauma patients. Trauma patients were younger than nontrauma (45.3 ± 19.4 vs. 61.1 ± 16.7, p < 0.0001). Nontrauma had higher simplified acute physiology score II compared with trauma patients (45.5 ± 16.3 vs. 41.1 ± 15.2, p = 0.009). Most prevalent pathogens in trauma patients with early VAP were Enterobacteriaceae spp. (46.9% vs. 27.8%, p = 0.06) followed by methicillin-susceptible Staphylococcus aureus (30.6% vs. 13%, p = 0.03) and then Haemophilus influenzae (14.3% vs. 1.9%, p = 0.02), and the most prevalent pathogen in late VAP was Acinetobacter baumannii (12.2% vs. 44.4%, p < 0.0001). Mortality was higher in nontrauma patients than in trauma patients (42.6% vs. 17.2%, p < 0.001, odds ratio [OR] = 3.55, 95%CI = 2.14-5.88). A logistic regression model adjusted for sex, age, severity of illness at intensive care unit admission, and sepsis-related organ failure assessment score at the day of VAP diagnosis confirmed that trauma was associated with a lower mortality compared with nontrauma patients (odds ratio [OR] = 0.37, 95%CI = 0.21-0.65). CONCLUSIONS: Trauma patients developing VAP had different demographic characteristics and episodes of etiology. After adjustment for potential confounders, VAP episodes in trauma patients are associated with lower mortality when compared with nontrauma patients.

Computer-assisted decision support for changing practice in severe sepsis and septic shock.

Computer-assisted decision support systems (CDSS) are designed to improve infection management. The aim of this prospective, clinical pre- and post-intervention study was to investigate the influence of CDSS on infection management of severe sepsis and septic shock in intensive care units (ICUs). Data were collected for a total of 180 days during two study periods in 2006 and 2007. Of the 186 patients with severe sepsis or septic shock, 62 were stratified into a low adherence to infection management standards group (LAG) and 124 were stratified into a high adherence group (HAG). ICU mortality was significantly increased in LAG versus HAG patients (Kaplan-Meier analysis). Following CDSS implementation, adherence to standards increased significantly by 35%, paralleled with improved diagnostics, more antibiotic-free days and a shortened time until antibiotics were administered. In conclusion, adherence to infection standards is beneficial for patients with severe sepsis or septic shock and CDSS is a useful tool to aid adherence.

Bronchial fistulae in ARDS patients: management with an extracorporeal lung assist device.

Patients with bronchial tree lesions feature, in particular, a high risk for developing bronchial fistulae after surgical repair when the clinical situation is complicated by acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mechanical ventilation is needed. The current authors hypothesised that extracorporeal carbon dioxide removal would significantly decrease inspiratory airway pressures, thus promoting the protection of surgical bronchial reconstruction. Four patients were studied after surgical reconstruction of bronchial fistulae in whom ALI/ARDS developed and mechanical ventilation with positive end-expiratory pressure was required. Gas exchange, tidal volumes, airway pressures, respiratory frequency, vasopressor and sedation requirements were analysed before and after initiation of a pumpless extracorporeal lung assist device (pECLA; NovaLung, Talheim, Germany). Initiation of pECLA treatment enabled a reduction of inspiratory plateau airway pressures from 32.4 to 28.6 cmH(2)O (3.2 to 2.8 kPa), effectively treated hypercapnia (from 73.6 to 53.4 mmHg (9.8 to 7.1 kPa)) and abolished respiratory acidosis (from pH 7.24 to 7.41). All patients survived and were discharged to rehabilitation clinics. In patients after surgical bronchial reconstruction that was complicated by acute lung injury/acute respiratory distress syndrome, use of pumpless extracorporeal carbon dioxide removal was safe and efficient. Initiation of a pumpless extracorporeal lung assist device enabled a less invasive ventilator management, which may have contributed to healing of surgical bronchial repair.

Regional hyperthermia of the abdomen in conjunction with chemotherapy for peritoneal carcinomatosis: evaluation of two annular-phased-array applicators.

BACKGROUND: Peritoneal carcinomatosis is a stage of gynecological and gastrointestinal malignancies with poor prognosis. Options for enhancing the effect of standard chemotherapy, such as aggressive surgery and intraperitoneal chemotherapy, have limitations. In this phase I/II study, we evaluated regional hyperthermia of the pelvis and abdomen using the annular-phased-array technique as an adjunct to chemotherapy. METHODS: Forty-five patients with peritoneal carcinomatosis (with or without liver metastases) in colorectal cancer (CRC) (n = 16), ovarian cancer (OC) (n = 17), or gastric/pancreatic/biliary cancer (n = 12) underwent standard chemotherapy and regional hyperthermia. Most CRC patients received second-line chemotherapy. All OC patients were platinum resistant. Regional hyperthermia was applied using a SIGMA-60 applicator (OC), a SIGMA-Eye/MR applicator (CRC), or various ring applicators (gastric/pancreatic/biliary cancer). RESULTS: Abdominal regional hyperthermia was well tolerated, with acceptable acute discomfort and no long-term morbidity. The SIGMA-Eye/MR applicator achieved higher systemic temperatures (associated with higher systemic stress) and more effective heating of the upper abdomen; the SIGMA-60 applicator achieved higher temperatures (and power densities) in the pelvis. Three-year overall survival was encouraging for patients with CRC (22%) and OC (29%) but not gastric/pancreatic/biliary cancer. For the SIGMA-60 applicator (patients with OC), higher measured temperatures at the vaginal stump correlated with better outcome. CONCLUSIONS. The SIGMA-60 and SIGMA-Eye/MR applicators are feasible for abdominal heating and have low toxicity. The SIGMA-60 applicator is specifically suitable for malignancies with high pelvic burden; the SIGMA-Eye/MR applicator better heats the upper abdomen, including the liver. Further randomized investigations are warranted.

Evidence-based therapy of severe acute respiratory distress syndrome: an algorithm-guided approach.

Despite considerable research and constantly emerging treatment modalities, the mortality associated with acute respiratory distress syndrome (ARDS) has remained virtually unchanged over the last decade. Clinical studies have been unable to show a reduction in mortality for most therapeutic interventions except for low tidal volume ventilation. Failure to prove a mortality benefit might be a result of the varying severity of ARDS in the patients studied. Nevertheless, positive responses to single supportive measures (inhaled nitric oxide, prone positioning and extracorporeal membrane oxygenation) have been demonstrated in multiple trials. Criteria for administration, weaning and discontinuation of these supportive interventions have never been described in detail. In this context, implementation of an evidence-based algorithm might facilitate clinical management of severe ARDS. This review summarizes the current evidence base and proposes a new treatment algorithm that aims to prioritize the administration of advanced strategies in a multimodal approach for ARDS.

Adherence to standard operating procedures is crucial for intensive care unit survival of elderly patients.

Elderly patients account for 42-52% of intensive care unit (ICU) admissions and for almost 60% of all ICU days in the USA and up to 50% receive inappropriate antibiotic treatment. The aim of this study was to evaluate whether adherence to Standard Operating Procedures (SOPs) reduced ICU mortality in an elderly population. The study included consecutive patients (n = 228) aged > or = 60 years with an ICU stay of > 72 h. SOPs were based on evidence-based medicine guidelines for diagnosis and treatment of infections, and on local resistance rates. According to preset indicators of quality management standards and assessment of different degrees of adherence, an implementation rate > 70% was considered adherent (high adherence group [HAG]) and < or = 70% was considered non-adherent (low adherence group [LAG]). Patients in the HAG (n = 137) had significantly reduced mortality compared with LAG patients (n = 91): 5.8% versus 19.8%, respectively. It was concluded that adherence to SOPs based on evidence-based medicine that consider local resistance rates for antibiotic treatment in elderly ICU patients is associated with a lower mortality rate.

Hyperactive delirium and blood glucose control in critically ill patients.

Delirium is a common complication of critically ill patients and is often associated with metabolic disorders. One of the most frequent metabolic disorders in intensive care unit (ICU) patients is hyperglycaemia. The aim of this retrospective study of 196 adult ICU patients was to determine if there is an association between hyperactive delirium and blood glucose levels in ICU patients. Hyperactive delirium was diagnosed using the delirium detection score. Blood glucose levels were monitored by blood gas analysis every 4 h. Hyperactive delirium was detected in 55 (28%) patients. Delirious patients showed significantly higher blood glucose levels than non-delirious patients Higher overall complication rates, length of ventilation, ICU stay and mortality rates were seen in the delirium group. In a multivariate analysis, glucose level, alcohol abuse, APACHE II score, complication by hospital-acquired pneumonia and a diagnosis of polytrauma on-admission all significantly influenced the appearance of delirium.

[Computed tomographic criteria as expected effect to inhaled nitric oxide in patients with severe acute respiratory distress syndrome]. / Computertomographische Kriterien für den zu erwartenden Effekt von inhaliertem Stickstoffmonoxid bei Patienten mit schwerem akutem Lungenversagen.

PURPOSE: Inhaled nitric oxide (iNO) is an effective therapy for severe hypoxemia in most patients with acute respiratory distress syndrome (ARDS). For unknown reason, a subset of ARDS patients does not respond favorably to iNO therapy. We hypothesized that radiological manifestation of lung injury may be related to iNO response. MATERIALS AND METHODS: We retrospectively analyzed data from n = 25 ARDS patients who received iNO, and underwent chest CT within 72 h prior to inhaled treatment. The morphology of coherently pathologic lung tissue was characterized by the length of the borderline between consolidated, infiltrated and atelectatic lung tissue and radiologically normal lung tissue. This quantity was expressed as relative fraction of the visceral pleural circumference and averaged over all CT slices. Furthermore we semiquantitatively determined the total volume of consolidated lung tissue as part of the whole lung. RESULTS: In n = 6 non-responders to iNO (DeltaPaO2 < 10 %), we determined a short relative borderline between normal and consolidated lung tissue due to the presence of large and coherently consolidated lung regions. In n = 19 iNO responders (DeltaPaO2 > 10 %), we found significantly less coherently consolidated lung tissue evidenced by an increased relative borderline when compared to iNO non-responders (0.09 +/- 0.02 vs. 0.1 +/- 0.01; P < 0.05). Moreover, there was a moderate and significant correlation between DeltaPaO2 induced by iNO and the relative borderline in all patients studied (R = 0.59; P < 0.05). Total fraction of consolidated lung tissue volume was not different between iNO non-responders and responders (60 +/- 3 % vs. 54 +/- 2 % n. s.). CONCLUSION: Our data demonstrate that the gross morphological distribution of pathological lung tissue influences iNO response in ARDS. Inhaled NO was most beneficial in injured lungs characterized by many small consolidated areas surrounded by normal lung tissue. The increased borderline between pathologic and normal lung tissue offers additional possibility for iNO to divert blood flow from shunt areas to ventilated lung regions, which consequently improves arterial oxygenation.