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Background: Although many predictive models have been developed to risk assess medical intensive care unit (MICU) readmissions, they tend to be cumbersome with complex calculations that are not efficient for a clinician planning a MICU discharge., Objective: To develop a simple scoring tool that comprehensively takes into account not only patient factors but also system and process factors in a single model to predict MICU readmissions., Design: Retrospective chart review., Participants: We included all patients admitted to the MICU of Robert Wood Johnson University Hospital, a tertiary care center, between June 2016 and May 2017 except those who were < 18 years of age, pregnant, or planned for hospice care at discharge., Main Measures: Logistic regression models and a scoring tool for MICU readmissions were developed on a training set of 409 patients, and validated in an independent set of 474 patients., Key Results: Readmission rate in the training and validation sets were 8.8% and 9.1% respectively. The scoring tool derived from the training dataset included the following variables: MICU admission diagnosis of sepsis, intubation during MICU stay, duration of mechanical ventilation, tracheostomy during MICU stay, non-emergency department admission source to MICU, weekend MICU discharge, and length of stay in the MICU. The area under the curve of the scoring tool on the validation dataset was 0.76 (95% CI, 0.68-0.84), and the model fit the data well (Hosmer-Lemeshow p = 0.644). Readmission rate was 3.95% among cases in the lowest scoring range and 50% in the highest scoring range., Conclusion: We developed a simple seven-variable scoring tool that can be used by clinicians at MICU discharge to efficiently assess a patient's risk of MICU readmission. Additionally, this is one of the first studies to show an association between MICU admission diagnosis of sepsis and MICU readmissions.

Introduction: Healthcare professionals who are directly involved in the diagnosis, treatment, and general care of patients with SARS-CoV-2 are at risk of developing adverse psychological reactions. A cross-sectional study of healthcare professionals aimed to determine the impact of the SARS-CoV-2 pandemic on the mental health of healthcare professionals in two of the largest referral hospitals in Athens, Greece., Methods: The study was conducted in the two largest SARS-CoV-2 referral hospitals in Athens, Greece. An assessment and the interrelationship of post-traumatic stress disorder, using the Impact of Event Scale-Revised [IES-R]) and burnout, using the Maslach Burnout Inventory [MBI]) was carried out., Results: A total of 162 subjects were enrolled in the study. Fifty-six (35%) had an IES-R score > 33, suggesting post-traumatic stress disorder. Forty-nine (30%) had an MBI score > 27. Seventy-five (46%) had a personal accomplishment score of < 33 and 46 (28%) had a depersonalization score >10. Stepwise backward logistic regression revealed that the only independent variable that was retained regarding the presence of post-traumatic stress disorder was the emotional exhaustion score of the MBI (at a cut-off of 24 in this scale, the 95% CI of the odds ratio for the presence of post-traumatic stress disorder was 1.077-1.173)., Conclusions: In this sample of first-line Greek healthcare professionals against SARS-CoV-2, most of them were proven to be quite resilient to this challenge. One-third of them had post-traumatic stress disorder, which depended on their degree of emotional exhaustion. Healthcare professionals, as represented by this study, performed their duties without feeling helpless and developing adverse psychological reactions., Competing Interests: Conflict of interest None to declare., (© 2021 Ioannis Ilias, Vassiliki Mantziou, Efstratios Vamvakas, Efstathia Kampisiouli, Maria Theodorakopoulou, Chariklia Vrettou, Evangelia Douka, Alice G. Vassiliou, Stylianos Orfanos, Anastasia Kotanidou, Ioanna Dimopoulou, published by Sciendo.)

#COVID19-induced ARDS is partly explained by the presence of microthrombi, motivating the use of thrombolytics. This study shows that thrombolytics decrease dead space ventilation in COVID-19 ARDS patients. https://bit.ly/2GdM44a., Competing Interests: Conflict of interest: S. Orfanos has nothing to disclose. Conflict of interest: I. El Husseini has nothing to disclose. Conflict of interest: T. Nahass has nothing to disclose. Conflict of interest: J. Radbel has nothing to disclose. Conflict of interest: S. Hussain has nothing to disclose., (Copyright ©ERS 2020.)

The aims of this study were to systematically review the literature on questionnaire-based group process measures and assess the psychometric scale development properties of these measures. A systematic search of questionnaire-based measures of group process was conducted from four databases: PsycINFO, Medline, EMBASE and AMED. A quality assessment was undertaken using established criteria. Only studies that described the development of questionnaire-based scales were included. Seventeen studies which described thirteen measures were included in the analysis. The developed list highlights a range of questionnaires that can be used by clinicians and researchers seeking to measure either "specific therapeutic group mechanisms" or "overall group experiences." Further research should focus on developing the content validity of these scales by involving the target population during item selection and reduction.

Frontotemporal dysconnectivity is a key pathology in schizophrenia. The specific nature of this dysconnectivity is unknown, but animal models imply dysfunctional theta phase coupling between hippocampus and medial prefrontal cortex (mPFC). We tested this hypothesis by examining neural dynamics in 18 participants with a schizophrenia diagnosis, both medicated and unmedicated; and 26 age, sex and IQ matched control subjects. All participants completed two tasks known to elicit hippocampal-prefrontal theta coupling: a spatial memory task (during magnetoencephalography) and a memory integration task. In addition, an overlapping group of 33 schizophrenia and 29 control subjects underwent PET to measure the availability of GABAARs expressing the α5 subunit (concentrated on hippocampal somatostatin interneurons). We demonstrate-in the spatial memory task, during memory recall-that theta power increases in left medial temporal lobe (mTL) are impaired in schizophrenia, as is theta phase coupling between mPFC and mTL. Importantly, the latter cannot be explained by theta power changes, head movement, antipsychotics, cannabis use, or IQ, and is not found in other frequency bands. Moreover, mPFC-mTL theta coupling correlated strongly with performance in controls, but not in subjects with schizophrenia, who were mildly impaired at the spatial memory task and no better than chance on the memory integration task. Finally, mTL regions showing reduced phase coupling in schizophrenia magnetoencephalography participants overlapped substantially with areas of diminished α5-GABAAR availability in the wider schizophrenia PET sample. These results indicate that mPFC-mTL dysconnectivity in schizophrenia is due to a loss of theta phase coupling, and imply α5-GABAARs (and the cells that express them) have a role in this process., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model., Methods: All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected., Results: In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ± 213.4 vs 193.5 ± 123.2, p < 0.001; 254.3 ± 70.6 vs 56.49 ± 16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice., Conclusions: In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The nongenomic mechanisms by which glucocorticoids modulate β 2 agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision-cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E 2 (PGE 2 ), cholera toxin (CTX), or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE 2 , or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation of myosin light chain, a necessary signaling event mediating force generation. In parallel studies, cAMP levels were augmented by simultaneous exposure of HASM cells to formoterol and budesonide. Budesonide, fluticasone, and prednisone alone rapidly increased cAMP levels, but steroids alone had little effect on bronchodilation in hPCLS. Bronchodilation induced by PGE 2 , CTX, or forskolin was also augmented by simultaneous exposure to budesonide in hPCLS. Furthermore, HASM cells expressed membrane-bound glucocorticoid receptors that failed to translocate with glucocorticoid stimulation and that potentially mediated the rapid effects of steroids on β 2 agonist-induced bronchodilation. Knockdown of glucocorticoid receptor-α had little effect on budesonide-induced and steroid-dependent augmentation of formoterol-induced cAMP generation in HASM. Collectively, these studies suggest that glucocorticoids amplify cAMP-dependent bronchodilation by directly increasing cAMP levels. These studies identify a molecular mechanism by which the combination of glucocorticoids and β 2 agonists may augment bronchodilation in diseases such as asthma or chronic obstructive pulmonary disease.

Pulmonary Arterial Hypertension is regarded as a devastating disease, complicating Connective Tissue Diseases. Although much progress has been achieved in the last 20 years, several unfulfilled needs in diagnosis and management of PAH in these patients may still be identified. After a systematic review of the literature and integrating results from the latest research articles, key clinical issues for the screening and diagnosis of Pulmonary Arterial Hypertension in Connective Tissue Disorder Patients and specifically Scleroderma patients are described in this article, allowing physicians to contribute to early diagnosis of patients with Scleroderma-associated Pulmonary Arterial Hypertension., (© 2019 The Mediterranean Journal of Rheumatology (MJR).)

Background: Non-attendance of treatment groups in the community has been a long-standing problem in mental health care. It has been found to have financial ramifications for services, worsen outcomes for those that do not attend and negatively impact on therapeutic group processes. There is a need to gain a better understanding of patients' reasons for attending or not attending. This study aimed to explore patient views on facilitators and barriers to the attendance of treatment groups in the community., Methods: The study used interview data collected as part of three studies that investigated treatment groups for psychiatric patients in the community. Sixty-seven interview transcripts were analysed using the framework method., Results: Five themes relating to facilitators of group attendance were identified: opportunity for autonomy; self-acknowledging need and therapist encouragement; optimal group format and safe environment; interest in content and enjoyment; actual and expected benefits of attendance. Four themes related to barriers: not being sufficiently informed; concerns about social interactions and the unknown; limited accessibility; and negative group dynamics., Conclusion: To facilitate attendance and reduce attrition to treatment groups in the community clinicians should address patient's wishes for information, capture their interest in the group modality, and potentially offer a 'trial' session. Furthermore, they should make the group location and time as accessible as possible and create a moderately sized group of six to eight patients. In these groups, mutual respect, feelings of safety and encouragement appear essential to make patients feel they can benefit from attendance., Competing Interests: The authors have declared that no competing interests exist.

The asthma-obesity syndrome represents a major public health concern that disproportionately contributes to asthma severity and induces insensitivity to therapy. To date, no study has shown an intrinsic difference between human airway smooth muscle (HASM) cells derived from nonobese subjects and those derived from obese subjects. The objective of this study was to address whether there is a greater response to agonist-induced calcium mobilization, phosphorylation of myosin light chain (MLC), and greater shortening in HASM cells derived from obese subjects. HASM cells derived from nonobese and obese subjects were age and sex matched. Phosphorylation of MLC was measured after having been stimulated by carbachol. Carbachol- or histamine-induced mobilization of calcium and cell shortening were assessed in HASM cells derived from nonobese and obese donors. Agonist-induced MLC phosphorylation, mobilization of calcium, and cell shortening were greater in obese compared with non-obese-derived HASM cells. The MLC response was comparable in HASM cells derived from obese nonasthma and nonobese fatal asthma subjects. HASM cells derived from obese female subjects were more responsive to carbachol than HASM cells derived from obese male subjects. Insulin pretreatment had little effect on these responses. Our results show an increase in agonist-induced calcium mobilization associated with an increase in MLC phosphorylation and an increase in ASM cell shortening in favor of agonist-induced hyperresponsiveness in HASM cells derived from obese subjects. Our studies suggest that obesity induces a retained phenotype of hyperresponsiveness in cultured human airway smooth muscle cells.

Background: Chronic Lung Allograft Dysfunction (CLAD) is the main cause of morbidity and mortality after the first year following lung transplantation (LTx). Risk factors of CLAD have been extensively studied, but the association between gram-negative bacteria (GNB) bronchial colonization and the development of CLAD is controversial. The purpose of our study was to investigate the association between post-transplant recolonization with the same species or de-novo colonization with a new GNB species and CLAD. The same analysis was performed on a sub-group of patients at the strain level using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry technique., Results: Forty adult cystic fibrosis (CF) patients who underwent a first bilateral LTx in the University Hospital of Marseille, between January 2010 and December 2014, were included in the study. Patients with GNB de-novo colonization had a higher risk of developing CLAD (OR = 6.72, p = 0.04) and a lower rate of CLAD-free survival (p = 0.005) compared to patients with GNB recolonization. No conclusion could be drawn from the subgroup MALDI-TOF MS analysis at the strain level., Conclusion: Post-LTx GNB airway recolonization seems to be a protective factor against CLAD, whereas de-novo colonization with a new species of GNB seems to be a risk factor for CLAD.

The human brain depends mainly on glucose supply from circulating blood as an energy substrate for its metabolism. Most of the energy produced by glucose catabolism in the brain is used to support intrinsic communication purposes in the absence of goal-directed activity. This intrinsic brain function can be detected with fMRI as synchronized fluctuations of the BOLD signal forming functional networks. Here, we report results from a double-blind, placebo controlled, cross-over study addressing changes in intrinsic brain activity in the context of very low, yet physiological, blood glucose levels after overnight fasting. Comparison of four major resting state networks in a fasting state and a state of elevated blood glucose levels after glucagon infusion revealed altered patterns of functional connectivity only in a small region of the posterior default mode network, while the rest of the networks appeared unaffected. Furthermore, low blood glucose was associated with changes in the right frontoparietal network after cognitive effort. Our results suggest that fasting has only limited impact on intrinsic brain activity, while a detrimental impact on a network related to attention is only observable following cognitive effort, which is in line with ego depletion and its reliance on glucose.

Within the cohort of patients suffering from idiopathic pulmonary arterial hypertension (IPAH) is a group that responds dramatically (VR-PAH) to an acute vasodilator challenge and that has excellent long-term hemodynamic improvement and prognosis on high dose calcium channel blockers compared with vasodilator non-responders (VN-PAH). For the purposes of diagnosing VR-PAH, there is to date no test to replace the acute vasodilator challenge. However, recent studies have identified markers that may aid in the identification of VR-PAH, including peripheral blood lymphocyte RNA expression levels of desmogelin-2 and Ras homolog gene family member Q, and plasma levels of provirus integration site for Moloney murine leukemia virus. Genome wide-array studies of peripheral blood DNA have demonstrated differences in disease specific genetic variants between VR-PAH and NR-PAH, with particular convergence on cytoskeletal function pathways and Wnt signaling pathways. These studies offer hope for future non-invasive identification of VR-PAH, and insights into pathogenesis that may lead to novel therapies. Examination of the degree of pulmonary microvascular perfusion in PAH has offered additional insights. During the acute vasodilator challenge, VR-PAH patients demonstrate true vasodilation with recruitment and increased perfusion of the capillary bed, while VN-PAH patients are unable to recruit vasculature. In the very few reports of lung histology, VR-PAH has more medial thickening in the precapillary arterioles, while VN-PAH has the classic histology of PAH, including intimal thickening. VR-PAH is a disorder with a phenotype distinct from VN-PAH and other types of PAH, and should be considered separately in the classification of PAH.

Introduction: Inhaled therapy is the mainstay of asthma treatment due to its local and rapid action. However, its efficiency relies on the teaching of a good inhalation technique by health care providers. We assessed health care providers' knowledge and practical skills in the use of inhalation devices., Methods: An observational multicenter study was conducted in the pulmonology and paediatric wards in Marseille. The departments' common practices, theoretical knowledge and practical skills were assessed through a questionnaire and a demonstration using a spacer device., Results: Forty health care providers were interviewed (9 attending physicians, 14 residents, 16 nurses and 1 physiotherapist), in 8 different pulmonology and paediatric wards. A total of 42.5% reported previous training in inhalation device technique. When evaluating theoretical knowledge, we found a mean of 54% correct answers. Attending physicians did significantly better than residents and nurses. With regard to practical skills, we found a mean of 1.12 failed steps out of 7. Here again attending physicians did significantly better than residents and nurses., Conclusion: Based on the results of our study, we recommend that attending physicians provide training of inhalation technique to nurses and residents, as they did significantly better theoretically and practically., (Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Surgical site infections (SSIs) and especially organ/space infection (O/SI) after resection or ablation of liver tumors are associated with increased morbidity and mortality. A secondary blood stream infection (BSI) is considered an O/SI but the exact prevalence is unknown. We aimed to investigate the incidence of O/SI and BSIs in a cohort of consecutive patients after liver resection or ablation, to seek for a possible connection between them and to search for potential risk factors., Materials and Methods: We reviewed all patients who underwent hepatic resection or intraoperative liver ablation between January 2012 and December 2016 in our department. We focused on age, gender, Child-Pugh score, preoperative biliary drainage, indication for surgery, type of resection, resection or ablation of tumor, need for bilioenteric reconstruction, additional procedure to hepatectomy, blood transfusion, operative time, postoperative admission to ICU, and antibiotic chemoprophylaxis. All positive cultures from intra-abdominal fluids and blood were recorded. O/SI and BSIs were diagnosed by the criteria set by Centers for Disease Control. All variables were compared between the group with O/SI and the group without infection. BSIs were associated with these infections also., Results: Eighty-one consecutive patients with a mean age of 64 years were enrolled. Fifteen patients presented a positive culture postoperatively: intra-abdominal fluid in eight, blood cultures in six, and both blood and intra-abdominal fluid in one patient. The directly estimated incidence of O/SI amounted to 11.1%. Four blood cultures were secondary to O/SI, and the remaining two secondary to central line catheter. O/SI was diagnosed indirectly, through the BSI in an additional 4.9% of the patients, raising the incidence of SSI to 16%. Among the factors studied, only admission to the ICU was found to be statistically significant as a risk factor for the development of O/SI ( p  = 0.026)., Conclusion: O/SI should be actively seeked for after liver surgery including blood cultures. Patients with affected physical status, comorbidities are in greater risk of developing O/SI.

Background: Obesity is a major worldwide public health issue. The main respiratory complication stemming from obesity is obesity hypoventilation syndrome (OHS). Most of the OHS patients diagnosed during an exacerbation are treated with non invasive ventilation (NIV). Up to date, no prospective study has demonstrated in real life conditions the feasibility of a systematic protocoled switch of NIV to continuous positive airway pressure (CPAP), once stability is achieved., Methods: In this prospective study, we included stable patients with OHS, with moderate to severe concomitant obstructive sleep apnea (OSA) and without obstructive pulmonary disease, who had been undergoing NIV for more than 2 months. The following measurements were performed, first with NIV and then after the switch to CPAP: diurnal arterial blood gas measurements; nocturnal oximetry and capnometry; mean compliance and AHI; measures of quality of life and quality of sleep., Results: 22/30 patients accepted to participate in the study and 15/22 patients completed the study. There were no significant differences for pooled data in diurnal alveolar blood gases, nocturnal capnometry (p = 0.534), nocturnal oximetry (p = 0.218), mean compliance (p = 0.766), mean AHI (p = 0.334), quality of life or quality of sleep. Eighty percent of the patients treated in this study favored CPAP over NIV., Conclusion: This pilot study showed in real life conditions the possibility of a systematic switch of NIV to CPAP, in most stable patients with OHS, with similar efficacy on diurnal and nocturnal alveolar gas exchange, quality of life and quality of sleep., Trial Registration: ISRCTN13981084 . Registered: 27 February 2017 (retrospectively registered).

Background: Research has shown that interactions in group therapies for people with schizophrenia are associated with a reduction in negative symptoms. However, it is unclear which specific interactions in groups are linked with these improvements. The aims of this exploratory study were to i) develop and test the reliability of using video-annotation software to measure interactions in group therapies in schizophrenia and ii) explore the relationship between interactions in group therapies for schizophrenia with clinically relevant changes in negative symptoms., Methods: Video-annotation software was used to annotate interactions from participants selected across nine video-recorded out-patient therapy groups (N = 81). Using the Individual Group Member Interpersonal Process Scale, interactions were coded from participants who demonstrated either a clinically significant improvement (N = 9) or no change (N = 8) in negative symptoms at the end of therapy. Interactions were measured from the first and last sessions of attendance (>25 h of therapy). Inter-rater reliability between two independent raters was measured. Binary logistic regression analysis was used to explore the association between the frequency of interactive behaviors and changes in negative symptoms, assessed using the Positive and Negative Syndrome Scale., Results: Of the 1275 statements that were annotated using ELAN, 1191 (93%) had sufficient audio and visual quality to be coded using the Individual Group Member Interpersonal Process Scale. Rater-agreement was high across all interaction categories (>95% average agreement). A higher frequency of self-initiated statements measured in the first session was associated with improvements in negative symptoms. The frequency of questions and giving advice measured in the first session of attendance was associated with improvements in negative symptoms; although this was only a trend., Conclusion: Video-annotation software can be used to reliably identify interactive behaviors in groups for schizophrenia. The results suggest that proactive communicative gestures, as assessed by the video-analysis, predict outcomes. Future research should use this novel method in larger and clinically different samples to explore which aspects of therapy facilitate such proactive communication early on in therapy.

Objectives: Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting., Methods: Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality., Results: In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004)., Conclusions: Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Despite promising findings from small-scale studies suggesting that body psychotherapy may be an effective treatment for negative symptoms, these results were not replicated in a recent multisite trial. In this trial a far smaller proportion of women were recruited relative to earlier studies, which may be an issue given the gender mix of the sample evaluated has been found to affect trial outcomes in schizophrenia. Using data from our multisite trial, the interaction between gender and treatment allocation as a predictor of outcomes was examined in 275 participants (72 women and 203 men) randomised to either a body psychotherapy or Pilates group. Negative symptoms were found to significantly reduce in women randomised to the body psychotherapy condition in comparison to Pilates, while no such effect was detected in men. Consistent with the smaller trials, this improvement was found to relate predominantly to expressive deficits. These findings suggest that body psychotherapy may be an effective treatment for negative symptoms in women. These findings emphasise the importance of sample characteristics in determining trial outcome in psychological treatment studies., Competing Interests: None, (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies.

Background: The reported incidence of hollow viscus injuries (HVI) in blunt trauma patients is approximately 1%. The most common site of injury to the intestine in blunt abdominal trauma (BAT) is the small bowel followed by colon, with mesenteric injuries occurring three times more commonly than bowel injuries. Isolated colon injury is a rarely encountered condition. Clinical assessment alone in patients with suspected intestinal or mesenteric injury after blunt trauma is associated with unacceptable diagnostic delays., Case Presentation: This is a case of a 31-year-old man, admitted to the emergency department after being the restrained driver, involved in a car accident. After initial resuscitation, focused assessment with sonography for trauma examination (FAST) was performed revealing a subhepatic mass, suspicious for intraperitoneal hematoma. A computed tomography scan (CT) that followed showed a hematoma of the mesocolon of the ascending colon with active extravasation of intravenous contrast material. An exploratory laparotomy was performed, hemoperitomeum was evacuated, and a subserosal hematoma of the cecum and ascending colon with areas of totally disrupted serosal wall was found. Hematoma of the adjacent mesocolon expanding to the root of mesenteric vessels was also noted. A right hemicolectomy along with primary ileocolonic anastomosis was performed. Patient's recovery progressed uneventfully., Conclusion: Identifying an isolated traumatic injury to the bowel or mesentery after BAT can be a clinical challenge because of its subtle and nonspecific clinical findings; meeting that challenge may eventually lead to a delay in diagnosis and treatment with subsequent increase in associated morbidity and mortality. Isolated colon injury is a rare finding after blunt trauma and usually accompanied by other intra-abdominal organ injuries. Abdominal 'seatbelt' sign, ecchymosis of the abdominal wall, increasing abdominal pain and distension are all associated with HVI. However, the accuracy of these findings remains low. Diagnostic peritoneal lavage, ultrasound, CT and diagnostic laparoscopy are used to evaluate BAT. Although CT has become the main diagnostic tool for this type of injuries, there are few pathognomonic signs of colon injury on CT. Given the potential for devastating outcomes, prompt diagnosis and treatment is necessary and high clinical suspicion is required.

Glucose metabolism serves as the central source of energy for the human brain. Little is known about the effects of blood glucose level (BGL) on higher-order cognitive functions within a physiological range (e.g., after overnight fasting). In this randomized, placebo-controlled, double blind study, we assessed the impact of overnight fasting (14 h) on brain activation during a working memory task. We sought to mimic BGLs that occur naturally in healthy humans after overnight fasting. After standardized periods of food restriction, 40 (20 male) healthy participants were randomly assigned to receive either glucagon to balance the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2-back and 0-back tasks, was used. Subclinically low BGL following overnight fasting was found to be linked to reduced involvement of the bilateral dorsal midline thalamus and the bilateral basal ganglia, suggesting high sensitivity of those regions to minimal changes in BGLs. Our results indicate that overnight fasting leads to physiologically low levels of glucose, impacting brain activation during working memory tasks even when there are no differences in cognitive performance., (© 2014 Wiley Periodicals, Inc.)

Background: The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in the septic process is under investigation. In this study, we assessed the role of sEPCR levels as an early indicator of sepsis development., Methods: Plasma sEPCR levels were measured in 59 critically-ill non-septic patients at the time of admission to the intensive care unit (ICU). Multiple logistic regression analysis was performed to identify potential risk factors for sepsis development and Cox-Regression models were fitted for variables to examine their relationship with time to sepsis development., Results: Thirty patients subsequently developed sepsis and 29 did not. At ICU admission, sequential organ failure assessment (SOFA) scores were significantly higher in the subsequent sepsis group as compared to the non sepsis group (mean ± SD: 6.4±2.7 and 5±2.3, respectively, P=0.037). sEPCR levels were also higher in the patients who subsequently developed sepsis compared to the patients who did not (median and interquartile range: 173.4 [104.5-223.5] ng/mL vs. 98.3 [69.8-147.7] ng/mL, respectively; P=0.004). Cox regression analysis identified sEPCR as the only parameter related to sepsis development with time (relative risk: 1.078, 95% confidence interval: 1.016-1.144, by 10 units; P=0.013)., Conclusion: Upon ICU admission, sEPCR levels in initially non-septic critically-ill patients appear elevated in the subjects who will subsequently become septic.

Background: Different psychotherapeutic treatments for schizophrenia are delivered in groups. However, little is known about the effectiveness of these group therapies for people with schizophrenia across different treatments with varying therapeutic orientations. This review aimed to (1) estimate the effect of different group psychotherapeutic treatments for schizophrenia and (2) explore whether any overall 'group effect' is moderated by treatment intensity, diagnostic homogeneity and therapeutic orientation., Methods: A systematic search of randomised controlled trials exploring the effectiveness of group psychotherapeutic treatments for people with schizophrenia was conducted. Random-effect meta-analyses on endpoint symptom scores compared group psychotherapeutic treatments with treatment as usual and active sham groups. Findings on social functioning were described narratively, and meta-regression analyses on group characteristics were carried out., Results: Thirty-four eligible trials were included. A weak-to-moderate significant between-group difference in favour of group psychotherapeutic treatments was found for negative symptom scores (standard mean difference = -0.37, 95% confidence interval -0.60, -0.14; p < 0.01, I(2) = 59.8%) only when compared to treatment as usual and not to active sham groups. Improved social functioning was reported as a treatment outcome in the majority of studies compared to treatment as usual. The 'group effect' on negative symptoms was positively related to 'treatment intensity' (β = 0.32, standard error = 0.121; p < 0.05)., Conclusion: Group psychotherapeutic treatments can improve negative symptoms and social functioning deficits in the treatment of schizophrenia. The effect occurs across different treatments and appears to be non-specific. Future research should identify the underlying mechanisms for the positive effect of participating in groups and explore how they can be maximised to increase the therapeutic benefit.

Objective: This study is in line with two previous ones from our group. They evaluated the influence of ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms [such as rs2230806 (R219K), rs2230808 (R1587K) and rs4149313 (I883M)] on the human lipid profile (defined as Optimal and Non-Optimal)., Methods: The present study included 447 unrelated young women and men self-reported as being healthy and that attended the University of Nursing of Technological and Educational Institution. All subjects were genotyped and the ABCA1 polymorphisms (R219K, R1587K and I883M) were recorded. According to lipid profile [total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C)] the subjects were separated into those with optimal lipid profile (Optimal Group, n=209) and Non-Optimal Group (n=238)., Results: No statistical differences were observed in the distribution of R219K, R1587K and I883M polymorphisms according to the lipid profile (p>0.05 in all cases). No statistical differences were observed in the distribution of R219K, R1587K and I883M polymorphisms according to sex (p>0.05 in all cases). However, Logistic Regression revealed that subjects with RK (R1587K polymorphism) genotype had 69% increased risk on average of having LDL-C above normal limits as compared with those with RR genotype. Similarly, subjects with K allele (R1587K polymorphism) had 59% increased risk on average of having LDL-C above normal limits compared with those with R allele., Conclusion: These findings suggest that R1587K polymorphism of ABCA1 gene may influence the lipid profile. However, this needs to be confirmed by larger studies.

Background: BMI is often used to evaluate the effectiveness of childhood obesity interventions, but such interventions may have additional benefits independent of effects on adiposity. We investigated whether benefits to health outcomes following the Mind, Exercise, Nutrition…Do It! (MEND) childhood obesity intervention were independent of or associated with changes in zBMI., Methods: A total of 79 obese children were measured at baseline; 71 and 42 participants were followed-up at 6 and 12 months respectively, and split into four groups depending on magnitude of change in zBMI. Differences between groups for waist circumference, cardiovascular fitness, physical and sedentary activities, and self-esteem were investigated., Results: Apart from waist circumference and its z-score, there were no differences or trends across zBMI subgroups for any outcome. Independent of the degree of zBMI change, benefits in several parameters were observed in children participating in this obesity intervention., Conclusion: We concluded that isolating a single parameter like zBMI change and neglecting other important outcomes is restrictive and may undermine the evaluation of childhood obesity intervention effectiveness.

Background: The aim of this paper was to investigate the effectiveness of three different recruitment maneuvers (RMs) on respiratory and hemodynamic indexes, in patients with acute respiratory distress syndrome (ARDS), and determine the impact of patients' body mass index (BMI) on RMs efficacy., Methods: This was a prospective clinical trial conducted in a general intensive care unit. In 25 consecutive early ARDS patients arterial blood gases, respiratory system elastance (Est,rs) and hemodynamics were monitored before (T(0)), and at 3, 15, and 30 min (T(3), T(15), T(30), respectively) after each of three different RMs techniques with same airway pressures (45 cmH(2)O), randomly applied in each patient; RM-1: pressure control ventilation for 1 min, RM-2: two hyperinflations with continuous positive airway pressure for 20 sec and 1 min interval in between, RM-3: three consecutive sighs., Results: All RMs improved oxygenation and Est,rs shortly (T(3)) after their application, but only RM-2 had a prolonged beneficial effect on oxygenation (T(30)). Patients were further divided according to their BMI: in the low BMI group (<27.3 Kg/m(2)) the effectiveness of RMs was similar to the whole study population, while in the high BMI group (≥ 27.3 Kg/m(2)) no sustained effect followed any RM., Conclusion: In our cohort, recruitment by two sustained inflations resulted in a more persistent improvement of oxygenation as compared with recruitment by pressure controlled ventilation or consecutive sighs with the same airway pressure. BMI seems to have an impact on RMs effectiveness, most probably by altering the effective transpulmonary pressure. More studies are required to elucidate this observation.

Background: In critically ill patients independent studies have shown contradictory findings regarding the prognostic significance of the D/D genotype of the I/D angiotensin converting enzyme (ACE) polymorphism. The study aim was to evaluate the effect of both ACE I/D polymorphism and ACE serum levels on the clinical outcomes of critically ill septic patients., Methods: This study recruited 186 Caucasian patients with sepsis, severe sepsis or septic shock. Epidemiological, clinical data, co-morbidities and severity scores were recorded. Measurements of serum ACE activity and genotyping for ACE I/D polymorphism were carried out. Primary outcomes were the 28- and the 90-day mortality; secondary outcomes included the number of days without renal or cardiovascular failure and ventilation-free days over the 28-day period following study enrolment., Results: Neither 28- nor 90-day mortality were associated with ACE I/D polymorphism (p=0.59 and 0.34, respectively) or circulating ACE levels (p=0.17 and 0.25, respectively). Similarly, ACE polymorphism and levels were not related to ventilation-free days (p=0.14 and 0.25, respectively), days without cardiovascular failure (p=0.14 and 0.81, respectively) and days without renal failure (p=0.64 and 0.27, respectively)., Conclusions: Neither ACE I/D polymorphism nor serum ACE levels seem to be significant prognostic factors of clinical outcomes in septic, critically ill patients.

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT >0.12 ng/mL [P<0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT >0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission., (Copyright © 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Aspergillus spp. infections mainly affect patients who are immunocompromised, and are extremely rare in immunocompetent individuals., Case Presentation: Aspergillus post-operative mediastinitis is considered to be a devastating infection, usually affecting patients undergoing cardiothoracic surgery with specific predisposing factors. We describe the case of an immunocompetent 68-year-old Caucasian man with severe chronic thromboembolic pulmonary hypertension, who underwent pulmonary thromboendarterectomy and developed post-operative mediastinitis due to Aspergillus flavus. The environmental control did not reveal the source of A. flavus infection and, despite combined antifungal therapy, our patient died as a result of septic shock and multiple organ failure., Conclusion: Aspergillus mediastinitis mainly affects patients after cardiosurgery operations with predisposing factors, and it is unusual in patients who are immunocompetent. The identification of the Aspergillus spp. source is often difficult, and there are no guidelines for the administration of pre-emptive therapy in this population of at-risk patients.

Genetic variants of hemostatic factors leading to prothrombotic phenotypes of hypercoagulability and hypofibrinolysis might affect prognosis of septic critically ill patients. Our aim was to evaluate the effect of four hemostatic genetic variants, namely fibrinogen-beta-455G/A, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphisms and factor V Leiden (FVL) mutation on survival of critically ill patients with severe sepsis or septic shock. A prospective, observational study in an 18-bed general ICU included 73 patients with severe sepsis or septic shock. Epidemiological, laboratory data and comorbidities along with severity scores were recorded. Genotyping for fibrinogen-beta-455G/A, FXIII V34L and PAI-1 4G/5G polymorphism and FVL mutation was carried out in all patients. The primary outcomes were the 28-day and the 90-day survival. Age, septic shock, severity indexes, prior steroid use and arterial pH were identified as predictors of the 28-day and 90-day survival in both the univariate and the multivariate models. On the contrary, none of the examined polymorphisms was found to significantly affect either the 28-day or the 90-day survival. Our data suggest that the importance of these hemostatic polymorphisms as predictors of the prognosis of sepsis in critically ill patients is probably very small.

Background: Procalcitonin (PCT) has been proposed as a diagnostic and prognostic sepsis marker, but has never been validated in febrile patients with prolonged ICU stay., Methods: Patients were included in the study provided they were hospitalised in the ICU for > 10 days, were free of infection and presented a new episode of SIRS, with fever >38 degrees C being obligatory. Fifty patients fulfilled the above criteria. PCT was measured daily during the ICU stay. The primary outcome was proven infection., Results: Twenty-seven out of 50 patients were diagnosed with infection. Median PCT on the day of fever was 1.18 and 0.17 ng/ml for patients with and without proven infections (p < 0.001). The area under the curve for PCT was 0.85 (95% CI; 0.71-0.93), for CRP 0.65 (0.46-0.78) and for WBC 0.68 (0.49-0.81). A PCT level of 1 ng/mL yielded a negative predictive value of 72% for the presence of infection, while a PCT of 1.16 had a specificity of 100%. A two-fold increase of PCT between fever onset and the previous day was associated with proven infection (p 0.001) (OR = 8.55; 2.4-31.1), whereas a four-fold increase of PCT of any of the 6 preceding days was associated with a positive predictive value exceeding 69.65%. A PCT value less than 0.5 ng/ml on the third day after the advent of fever was associated with favorable survival (p 0.01)., Conclusion: The reported data support that serial serum PCT may be a valuable diagnostic and prognostic marker in febrile chronic critically ill patients.

Background: Several reports have shown that homocysteine promotes thrombosis by disturbing the procoagulant-anticoagulant balance, whereas alterations in coagulation and fibrinolysis have been suggested as important pathogenetic and prognostic determinants of mortality in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The objective of the study was to evaluate the effect of plasma homocysteine levels on the outcomes of patients with ALI/ARDS., Methods: Sixty-nine consecutive ventilated patients with ALI/ARDS were studied. Blood samples were drawn within 3 days of clinical recognition of ARDS. Measurement of plasma homocysteine, vitamin B12, folate, creatinine, protein C and plasminogen-activator inhibitor-1 antigen levels, and genotyping of the methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms were carried out. The primary outcomes were 28- and 90-day mortality, whereas secondary outcomes included nonpulmonary organ failure-free days, liberation from mechanical ventilation up to day 28, and ventilator-free days during the 28 days after enrollment., Results: In the multivariable analysis, plasma homocysteine concentration adjusted for age, Acute Physiology and Chronic Health Evaluation II score, methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and levels of plasminogen-activator inhibitor-1 antigen, protein C, creatinine, vitamin B12, and folate was not found to affect significantly mortality at 28 and 90 days (P = 0.39 and P = 0.83, respectively), days without organ failure besides lungs (P = 0.38), the probability of being free from mechanical ventilation at day 28 (P = 0.63), and days without ventilation assistance (P = 0.73)., Conclusion: Our data suggest that increased plasma homocysteine levels, either alone or in synergy with other thrombophilic risk factors, do not seem to adversely affect the prognosis in patients with ALI/ARDS.

Introduction: Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS., Materials and Methods: 52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days., Results: 17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p=0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio=9.95, 95% CI: 1.79-55.28, p=0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p=0.033 and p=0.008, respectively)., Conclusions: ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.

Objectives: To describe the concentrations of sTREM-1 in patients with sepsis and to explore the effects of their serum on the expression of TREM-1 on U937 monocytes., Methods: Blood was sampled at regular time intervals in 56 patients with sepsis. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1alpha), IL-6, IL-8, IL-10 and IL-12p70 and sTREM-1 were measured. U937 monocytes were incubated in the presence of serum at sepsis onset., Results: Median sTREM-1 concentration on day 1 for patients with septic shock was 915 pg/ml and 228.5 pg/ml for those without shock (p = 0.002). TNFalpha, IL-1alpha, IL-6, IL-8 and IL-10 did not differ between them. A positive correlation was found between changes of sTREM-1 and SOFA scores from day 1 to 7. Sera of patients with septic shock evoked a significant increase of the expression of TREM-1. The concentrations of TNFalpha and IL-8 in supernatants increased only after stimulating with sera of patients without shock, but not after stimulating with sera of patients with shock., Conclusions: Levels of sTREM-1 correlated with sepsis severity. sTREM-1 is considerably higher in patients with shock compared to patients without shock. The serum of shocked patients could stimulate the expression of TREM-1 on U937 monocytes.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) causes physical plugging of large pulmonary arteries as well as a distal micro-vasculopathy. Pulmonary endothelium is an active metabolic tissue in normal humans. The effects of CTEPH on pulmonary endothelial metabolism are unknown., Objectives: We studied pulmonary capillary endothelium-bound angiotensin converting enzyme (ACE) activity as an index of endothelial metabolism in patients with CTEPH., Patients/methods: We measured single-pass transpulmonary per cent metabolism (%M) and hydrolysis of an ACE synthetic substrate and calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), in 13 patients with CTEPH and 23 controls., Results: Mean %M for CTEPH (71.6 +/- 4.0% SE) was similar to controls (74.7 +/- 2.7%). Substrate hydrolysis (v) was similar for CTEPH (1.47 +/- 0.22) and controls (1.51 +/- 0.11). However, FCSA/BSA was reduced (P < 0.01) for CTEPH (1530 +/- 218 mL min(-1)*m(-2)) as compared with controls (2948 +/- 245)., Conclusions: The metabolically functional pulmonary capillary bed is reduced in CTEPH. However, because %M and hydrolysis are preserved, this points to a reduction in functional capillary surface area rather than reduced ACE activity on the pulmonary capillary endothelial cell. The reduction in functional capillary surface area may just be a result of decreased capillary recruitment because of upstream vascular plugging by chronic organized thrombus.

Objective: Perioperative pituitary-adrenal responses after major abdominal surgery have not been well characterized. The aim of the present study was to further clarify perioperative pituitary-adrenal responses., Design: Thirty-six patients (20 men), aged 68+/-10 years (mean+/-SD), undergoing major abdominal operations were studied. Total cortisol (TC), adrenocorticotropic hormone (ACTH), corticosteroid-binding globulin (CBG), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) were measured preoperatively (PreOp), on the day of surgery (DoS) and on the first and second postoperative days (PoD1 and PoD2). The free cortisol index (FCI) was also calculated. In addition, patients underwent a low-dose (1 mug) ACTH stimulation test, preoperatively and on PoD1, to assess adrenal responsiveness to ACTH., Results: TC, FCI, ACTH and DHEA were increased, while DHEAS and CBG declined on DoS compared to PreOp levels. On PoD1, plasma ACTH was lower compared to the preoperative levels, FCI remained elevated, DHEA, DHEAS and TC returned to their baseline values, while CBG was still low. On PoD2, ACTH and CBG were low and FCI returned to its PreOp levels. Postoperatively, stimulated FCI was higher compared to the PreOp value., Conclusion: At an early phase following major surgery, elevated cortisol is associated with high ACTH. Despite HPA activation and a concomitant rise in DHEA levels, DHEAS declines. Later on, a remarkable dissociation between ACTH (low) and cortisol (high) is observed, which is attributed, at least in part, to increased adrenal responsiveness to ACTH.

Purpose: To determine the inter-relationships between cytokine levels and physiological scores in predicting outcome in unselected, critically ill patients., Methods: To this end, 127 patients (96 men), having a mean+/-SD age of 45+/-20 years, with a wide range in admission diagnoses (medical, surgical, and multiple trauma patients) were prospectively investigated. Severity of critical illness and organ dysfunction were graded by acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores, respectively. Blood samples were drawn on admission in the ICU to determine pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10. The main outcome measure was 28-day mortality., Results: Overall, 88 patients survived and 39 patients died. Univariate logistic regression analysis showed that SOFA, APACHE II, IL-8, IL-6, and IL-10 on admission in the ICU were related to mortality. Multiple logistic regression analysis in the entire cohort of critically ill patients revealed that SOFA (OR=1.341, p<0.001) and IL-6 (OR=1.075, p=0.01) constituted independent outcome predictors. receiver operator characteristics curve analysis showed that SOFA, APACHE II, and IL-6 had the highest area under the curve values. IL-6 correlated with APACHE II (r(s)=0.44, p<0.0001) and SOFA (r(s)=0.40, p<0.0001) scores., Conclusions: In mixed ICU patients cytokine concentrations on admission in the ICU represent independent outcome predictors in the presence of disease severity scores.

Objective: To assess whether adrenal cortex hormones predict ICU mortality in acute, mixed, critically ill patients., Design and Setting: Prospective study in consecutive intensive care patients in the general ICU of a teaching hospital., Patients: 203 severely ill patients with multiple trauma (n = 93), medical (n = 57), or surgical (n = 53) critical states., Measurements and Results: Within 24 h of admission in the ICU a morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and dehydropiandrosterone sulfate (DHEAS). Subsequently a low-dose (1 microg) ACTH test was performed to determine stimulated cortisol. The incremental rise in cortisol was defined as stimulated minus baseline cortisol. Overall, 149 patients survived and 54 died. Nonsurvivors were older and in a more severe critical state, as reflected by higher SOFA and APACHE II scores. Nonsurvivors had a lower incremental rise in cortisol (5.0 vs. 8.3 microg/dl and lower DHEAS (1065 vs. 1642 ng/ml) than survivors. The two groups had similar baseline and stimulated cortisol. Multivariate logistic regression analysis revealed that age (odds ratio 1.02), SOFA score (1.36), and the incremental rise in cortisol (0.88) were independent predictors for poor outcome., Conclusions: In general ICU patients a blunted cortisol response to ACTH within 24 h of admission is an independent predictor for poor outcome. In contrast, baseline cortisol or adrenal androgens are not of prognostic significance.

Objective: To evaluate whether tentative prognostic models for intensive care unit survival of multiple trauma patients could be improved by including endocrine parameters., Design: Prospective study., Patients: Eighty-three male and 11 female multiple trauma patients., Measurements: Upon admission, severity of trauma was assessed with the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Sequential Organ Failure Assessment (SOFA) score and the Injury Severity Score (IS). Concurrently, blood was drawn to measure thyrotropin (TSH), free thyroxine (fT4), trioodothyronine (T3), corticotropin (ACTH), prolactin (PRL), cortisol and dehydroepiandrosterone sulphate (DHEAS). Adrenal reserve was assessed with the Synacthen test., Results: Seventy-five of the 83 men and 8 of the 11 women survived. APACHE II and SOFA scores were higher in non-survivors compared to survivors (with considerable overlap). From the baseline endocrine work-up, survivors had higher ACTH and DHEAS values compared to non-survivors (also with considerable overlap). No differences between survivors and non-survivors were noted in the Synacthen test or in thyroid function tests. Nevertheless, a multivariate logistic regression model that incorporated the APACHE II score and hormonal parameters (Cortisol post-Synacthen, DHEAS, TSH*age) was well-fitted to assess survival/non-survival as an endpoint and better than APACHE II, SOFA or IS scores alone to predict ICU survival or death., Conclusion: In critically ill multiple trauma patients, age, TSH, Cortisol post-Synacthen and DHEAS values upon admission to the ICU, combined with the APACHE II score, may predict outcome more accurately than the APACHE II score alone.an the APACHe II score alone.

Objective: To investigate the pattern of pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in critically ill patients and to examine the relation between responses and clinical outcome., Design and Setting: Prospective study in consecutive critically ill patients in a general intensive care unit in a teaching hospital., Patients: The study included 37 critically ill, mechanically ventilated patients with diverse underlying diagnoses (28 men, 9 women; median age 56 years)., Interventions: A morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and cytokines. Patients were then injected with 100 microg hCRH, and plasma cortisol and ACTH were measured over a period of 2 h., Measurements and Results: In the overall patient population baseline and peak cortisol concentrations following hCRH were 16+/-5 and 21+/-5 microg/dl, respectively, and median baseline and peak ACTH levels 23 and 65 pg/ml, respectively. Higher ACTH levels and longer release of cortisol were noted in nonsurvivors (n=18) than in survivors (n=19). Furthermore, nonsurvivors had higher concentrations of interleukin 8 (115 vs. 38 pg/ml) and interleukin 6 (200 vs. 128 pg/ml) than survivors., Conclusions: Critically ill patients demonstrate altered pituitary-adrenal axis responses to hCRH. This is particularly evident in the sickest patients with the highest degree of inflammatory profile who ultimately do not survive.

The chemotactic factor formyl-methionyl-leucyl-phenylalanine (FMLP) when injected in rabbits causes dose-dependent transient hypotension, as well as neutropenia, thrombocytopenia and a decrease in systemic vascular resistance, as previously shown. Since both FMLP and endotoxin are elaborated at sites of infection by certain bacteria, whether they act in concert to produce shock was examined. Animals were pretreated with 380 microg/kg of E. coli endotoxin, 24 hours before the infusion of 10(-9) moles FMLP and were compared with animals pretreated only with saline and administered FMLP. Within 3 min after FMLP, endotoxin-pretreated animals developed a significant fall in MAP (p < 0.001) and neutrophils (p < 0.001) compared to controls. Statistically significant lactic acidemia, with reduced HCO(-)3 levels also developed in the endotoxin-pretreated group after FMLP injection. These results indicate that endotoxin apparently induces a prepared state, thus facilitating the hemodynamic and cellular effects of FMLP in this model.

To establish whether cytokine release is implicated in thyroid hormone changes during surgical stress we studied 36 adult patients (20 men; mean age +/- SD: 68.5 +/- 10.5 years) undergoing elective major abdominal operations. We measured tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8 and IL-10 and thyrotropin (TSH), free thyroxine (FT(4)) and triiodothyronine (T(3)) before scheduled non-emergency surgery, immediately postoperatively, on the 1st postoperative day (post-1) and on the 2nd postoperative day (post-2). TNF-alpha, IL-6 and IL-8 peaked on day post-1 whereas IL-10 peaked immediately postoperatively. Fourteen of 36 patients had low T(3) levels after surgery, indicating non-thyroidal illness (NTI). Significant negative correlations were noted among TNF-alpha, IL-6 and IL-8 against T(3) and FT(4). Cytokines are responsible, at least in part, for NTI following major operations., ((c) 2007 S. Karger AG, Basel)

Objective: To assess respiratory mechanics on the 1st and 5th days of mechanical ventilation in a cohort of brain-damaged patients on positive end-expiratory pressure (PEEP) of 8 cmH(2)O or zero PEEP (ZEEP)., Design and Setting: Physiological study with randomized control trial design in a multidisciplinary intensive care unit of a university hospital., Patients and Measurements: Twenty-one consecutive mechanically ventilated patients with severe brain damage and no acute lung injury were randomly assigned to be ventilated with ZEEP (n = 10) or with 8 cmH(2)O of PEEP (n = 11). Respiratory mechanics and arterial blood gases were assessed on days 1 and day 5 of mechanical ventilation., Results: In the ZEEP group on day 1 static elastance and minimal resistance were above normal limits (18.9 +/- 3.8 cmH(2)O/l and 5.6 +/- 2.2 cmH(2)O/l per second, respectively); on day 5 static elastance and iso-CO(2) minimal resistance values were higher than on day 1 (21.2 +/- 4.1 cmH(2)O/l; 7.0 +/- 1.9 cmH(2)O/l per second, respectively). In the PEEP group these parameters did not change significantly. One of the ten patients on ZEEP developed acute lung injury. On day 5 there was a significant decrease in PaO(2)/FIO(2) in both groups., Conclusions: On day 1 of mechanical ventilation patients with brain damage exhibit abnormal respiratory mechanics. After 5 days of mechanical ventilation on ZEEP static elastance and minimal resistance increased significantly, perhaps reflecting "low lung volume" injury. Both could be prevented by administration of moderate levels of PEEP.