Autoimmune Polyendocrine Syndromes in Adult Italian Celiac Disease Patients.

Celiac disease (CD) is frequently associated with other autoimmune disorders. Different studies have explored the association between CD and single autoimmune endocrine disease (AED), especially autoimmune thyroiditis (AIT) and type-1 diabetes mellitus (T1DM). Data about CD as a component of autoimmune polyendocrine syndrome (APS) are scant. We analyzed a large dataset including prospectively collected data from 920 consecutive adult CD patients diagnosed in a third-level Italian institution in the 2013-2023 period, The prevalence of isolated autoimmune endocrine diseases and APS were collected. A total of 262 (28.5%) CD patients had at least one associated AED, with AIT (n = 223, 24.2%) and T1DM (n = 27, 2.9%) being the most frequent conditions. In most cases (n = 173, 66%), AEDs were diagnosed after CD. Thirteen patients (1.4%) had at least two of the requested three endocrinopathies, satisfying the diagnosis of type 2 APS. APS-2 is a rare but not exceptional occurrence among Italian CD patients, underscoring the intricate and multifaceted nature of autoimmune disorders. Periodic evaluations of thyroid function and glycaemia should be recommended after the diagnosis of CD together with testing for autoantibodies that may be helpful in assessing disease risk before disease onset. Likewise, implementation of a systematic screening for CD amongst T1DM and other autoimmune endocrine diseases are paramount.

Evolution of bone densitometry parameters and risk of fracture in coeliac disease: a 10-year perspective.

BACKGROUND: Metabolic bone disease is frequently found in patients with coeliac disease (CD). Despite its high prevalence, international guidelines are partially discordant about its management due to the lack of long-term data. METHODS: We retrospectively evaluated a large dataset of prospectively collected data of CD patients assessing the variation of DXA parameters and estimated fracture risk according to the FRAX® score in a 10-year follow-up. Incident fractures are reported, and the predictive ability of the FRAX® score is verified. RESULTS: We identified 107 patients with low bone density (BMD) at the diagnosis of CD and a 10-year follow-up. After improving at the first follow-up, T-scores slowly reduced over time but with no clinically relevant differences between the first and last examination (lumbar spine: from - 2.07 to - 2.07, p = 1.000; femoral neck: from - 1.37 to - 1.55, p = 0.006). Patients with osteoporosis at the index measurement had more marked fluctuations than those with osteopenia; the latter group also showed minimal modifications of the FRAX® score over time. Six incident major fragility fractures occurred, with a good predictive ability of the FRAX® (AUC 0.826). CONCLUSION: Adult CD patients with osteopenia and no risk factors had substantially stable DXA parameters and fracture risk during a 10-year follow-up. A dilated interval between follow-up DXA for these patients could be considered to reduce diagnosis-related time and costs, maintaining a 2-year interval for patients with osteoporosis or risk factors.

Low haemoglobin level predicts early hospital readmission in patients with cirrhosis and acute decompensation.

Background & Aims: Patients with decompensated cirrhosis present frequent hospitalisations with a relevant clinical and socio-economic impact. This study aims to characterise unscheduled readmissions up to 1-year follow-up and identify predictors of 30-day readmission after an index hospitalisation for acute decompensation (AD). Methods: We performed a secondary analysis of a prospectively collected cohort of patients admitted for AD. Laboratory and clinical data at admission and at discharge were collected. Timing and causes of unscheduled readmissions and mortality were recorded up to 1 year. Results: A total of 329 patients with AD were included in the analysis. Acute-on-chronic liver failure was diagnosed in 19% of patients at admission or developed in an additional 9% of patients during the index hospitalisation. During the 1-year follow-up, 182 patients (55%) were rehospitalised and 98 (30%) more than once. The most frequent causes of readmission were hepatic encephalopathy (36%), ascites (22%), and infection (21%). Cumulative incidence of readmission was 20% at 30 days, 39% at 90 days, and 63% at 1 year. Fifty-four patients were readmitted for emergent liver-related causes within 30 days. Early readmission was associated with a higher 1-year mortality (47 vs. 32%, p = 0.037). Multivariable Cox regression analysis showed that haemoglobin (Hb) ≤8.7 g/dl (hazard ratio 2.63 [95% CI 1.38-5.02], p = 0.003) and model for end-stage liver disease-sodium score (MELD-Na) >16 at discharge (hazard ratio 2.23 [95% CI 1.27-3.93], p = 0.005), were independent predictors of early readmission. In patients with MELD-Na >16 at discharge, the presence of Hb ≤8.7 g/dl doubles the risk of early rehospitalisation (44% vs. 22%, p = 0.02). Conclusion: Besides MELD-Na, a low Hb level (Hb ≤8.7 g/dl) at discharge emerged as a new risk factor for early readmission, contributing to identification of patients who require closer surveillance after discharge. Impact and Implications: Patients with decompensated cirrhosis face frequent hospitalisations. In the present study, type and causes of readmissions were analysed during 1-year follow-up in patients discharged after the index hospitalisation for an acute decompensation of the disease. Early (30-day) liver-related readmission was associated with higher 1-year mortality. The model for end-stage liver disease-sodium score and low haemoglobin at discharge were identified as independent risk factors for early readmissions. Haemoglobin emerged as a new easy-to-use parameter associated with early readmission warranting further investigation.

Hepatic Steatosis in Patients with Celiac Disease: The Role of Packaged Gluten-Free Foods.

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice. Methods: We administered a simple questionnaire based on a Recency, Frequency, and Monetary value (RFM) analysis (a cornerstone of direct marketing segmentation) to consecutive CD patients on a GFD for >6 months and verified its association with NAFLD. Subgroup analyses were performed to understand whether specific patterns of PGFF consumption were significantly associated with NAFLD. Results: Amongst 147 patients (female 82%, median age 42 years), 45 (30.6%) had NAFLD. Total RFM score (adjusted odds ratio = 1.223, 95% CI: 1.059−1.413, p = 0.006), body mass index, and total cholesterol and triglycerides were independently related to NAFLD, and "Bread and bakery" (p = 0.002), "salty convenience" (p = 0.005), and "sweet convenience" (p = 0.049) products were significantly related with NAFLD. Also, questions about the number of purchased PGFF in the last month (monetary value) and different categories of PGFF consumed in the last week (recency) were particularly able to identify NAFLD patients. Conclusions: The specific GFD dietary habits of CD patients were correlated with the degree of risk of NAFLD. Information was obtained through a questionnaire which could be used in clinical practice to favor a patient-tailored approach and in future studies to verify the reproducibility of our results in different geographical areas.

Risk of Drop-Out from Follow-Up Evaluations for Celiac Disease: Is It Similar for All Patients?

Background: Celiac disease (CD) follow-up is a relatively underevaluated topic. However, correct adherence to follow-up procedures is central to the early recognition of complicated CD and other conditions typically associated with CD. Establishing whether patients at increased risk of complications follow clinicians' recommendations has multiple repercussions. Methods: We retrospectively analyzed the records of patients consecutively diagnosed with CD in our outpatient clinic between January 2004 and October 2017 to investigate the factors associated with drop-out from follow-up procedures. Results: Among the 578 patients analyzed, 40 (6.9%) dropped out during the first six months and 272 (50.6%) during the observation period. The median time to drop-out was 7.4 years (95% confidence interval: 6.8−8.0). No factors were associated with early drop-out. Instead, age at diagnosis >40 years (40−59 years, p < 0.001; ≥60 years, p = 0.048) and classical clinical presentation (p = 0.016) were significantly associated with a lower risk of later drop-out. Conclusions: Patients at increased risk of complicated CD are more compliant with follow-up procedures than patients at lower risk, despite being prescribed the same controls. These results indirectly support the hypothesis of tailored follow-up strategies, differentiated according to the risk of complications.

Efficacy of a short course of lung ultrasound for primary care physicians in the assessment of COVID-19-positive patients.

INTRODUCTION: Lung ultrasound (LUS) has become the first diagnostic imaging approach to assess lung involvement in COVID-19. While LUS proved to be safe, reliable, and accurate, not many primary care physicians (PCP) are capable to employ this instrument in the first evaluation of COVID-19 outpatients. The aim of this study was to determine the effectiveness of a brief training program in LUS for PCP. METHODS: Italian local authorities promoted a training program in LUS for PCP engaged in COVID-19 outpatients' evaluation. The course took place in a COVID-19 unit and included a hands-on practice on real COVID-19 patients. We conducted a qualitative and quantitative analysis of the results of the training program. RESULTS: A total of 32 PCP completed the training. About 100% of participants reported an increase in competence and confidence in the use of LUS after the training. Self-reported confidence in detecting major COVID-19 LUS abnormalities was high (B-lines 8/10, pleural abnormalities 6.5/10). B-lines were accurately identified with a reliability of 81%, with a sensitivity of 96%, and a negative predictive value of 98%. Trainees were some less accurate in detecting pleural abnormalities (reliability 63%) but with a high specificity (99%). CONCLUSIONS: This study showed that a short training program, but comprising a hands-on practice, is capable to bring even almost novices to achieve a high overall accuracy and reliability in detecting lung involvement in COVID-19. This may result in a significant improvement of the performances of PCP involved in the first evaluation of COVID-19 cases in primary care facilities.

Occurrence of ventilator associated pneumonia using a tracheostomy tube with subglottic secretion drainage.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality in critically ill patients who require mechanical ventilation (MV). Subglottic secretions above the endotracheal cuff are associated with bacteria colonization of lower respiratory tract, causing VAP. A preventive strategy to avoid subglottic secretion progression is the drainage with special tracheal tubes effective in preventing both early onset and late onset VAP. The purpose of this study was to measure VAP incidence in tracheostomized patients with suction above the cuff. METHODS: The authors performed a matched cohort study with historical control in three academic Intensive Care Units (ICUs): upon ICU admission, patients requiring MV were submitted to tracheostomy with a tracheal tube allowing drainage of subglottic secretions (treatment group). A control group without suctioning above the cuff was selected applying the propensity score matching on dataset of previous ELT Study. VAP occurrence at 28-days from intubation was the primary endpoint; hospital mortality and ICU-free days at 28-days were the secondary endpoints. RESULTS: Between July 2014 and April 2016, 125 tracheostomized patients were included in the analysis. 232 tracheostomized patients without suctioning were selected as a control group for the matched cohort study. The application of propensity score matching selected 60 patients to compare the two groups. Incidence of VAP was 8% in treatment group and 19.4% in the control group (P value =0.004). After balance with propensity score matching VAP was 8.3% and 21.7% (P value =0.0408), respectively. CONCLUSIONS: Subglottic secretion drainage reduces incidence of VAP in critically ill patients requiring ongoing MV via tracheostomy.

Long term effects of gluten-free diet in non-celiac wheat sensitivity.

BACKGROUND & AIMS: Information about the clinical outcome of patients with non-celiac wheat sensitivity (NCWS) treated with gluten-free diet (GFD) derive from studies assessing the symptom response in the first few weeks of treatment. We aimed to evaluate the clinical response to the GFD and the quality of life (QoL) of NCWS patients in the long term. METHODS: Forty-four NCWS (diagnosed according to the Salerno criteria) participated in the study. Participants rated their symptoms according to a 0-10 scale patients and filled in a QoL questionnaire (CDQ) before the beginning of the GFD and during a follow-up evaluation performed after at least one year. To assess the reliability of the questionnaire we also included a control group of 43 matched patients with celiac disease (CD). RESULTS: Upon diagnosis, NCWS patients had a high prevalence of intestinal and extraintestinal symptoms. Also, most symptoms were described as severe and the QoL questionnaire showed high scores. On follow-up, both prevalence and severity of the most common symptoms were significantly reduced. However, persistent intestinal and extraintestinal symptoms of mild severity were found in 65.9 and 72.7% of NCWS patients. In comparison, in the CD group, the prevalence was lower (32.6 and 23.2% respectively) and consistent with previous studies. The analyses of the determinant of QoL showed that, upon diagnosis, NCWS patients had higher scores in the CDQ "gastrointestinal symptoms" (p < 0.001), "emotional aspects" (p < 0.001) and "social problems" (p < 0.001) subclasses compared to CD patients. After the GFD, NCWS and CD patients shared similar scores in all of the subclasses. CONCLUSIONS: A significant proportion of NCWS patients still complains of intestinal and extraintestinal symptoms, even if significantly attenuated by the GFD, even years after the diagnosis. A comprehensive nutritional evaluation of these patients is required to further improve their symptoms and their QoL.

Celiac Disease Diagnosed through Screening Programs in At-Risk Adults Is Not Associated with Worse Adherence to the Gluten-Free Diet and Might Protect from Osteopenia/Osteoporosis.

Screening strategies to detect celiac disease (CD) in at-risk subjects are of paramount importance to prevent the possible long-term complications of this condition. It is therefore of strategic relevance to understand whether patients diagnosed through screening follow a strict gluten-free diet (GFD), as the non-compliance to this diet can make screening efforts pointless. Currently, no studies have verified whether CD patients diagnosed in their adulthood are adhering to the GFD years after the diagnosis. We retrospectively evaluated the medical records of 750 CD patients diagnosed in our center during January 2004⁻December 2013 to verify differences between screening detected and clinically diagnosed patients. The groups shared a similar adherence to the GFD (91.2 versus 89.8%, p = 0.857). Moreover, the rates of non-responsive CD, GFD-induced metabolic alterations, and persistence in controls were also similar. Instead, screening-detected patients had a significantly lower rate of osteopenia/osteoporosis at diagnosis (31.3 versus 46%, p < 0.001). In conclusion, screening strategies for CD in at-risk groups should be encouraged even in the adult population. Patients diagnosed through these strategies had no additional problems compared to those diagnosed for clinical suspicion and might benefit from a protective effect against metabolic bone disease.

Systemic treatments for hepatocellular carcinoma: challenges and future perspectives.

Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.

Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study.

Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively). CONCLUSION: Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.

Haptic, Virtual Interaction and Motor Imagery: Entertainment Tools and Psychophysiological Testing.

In this work, the perception of affordances was analysed in terms of cognitive neuroscience during an interactive experience in a virtual reality environment. In particular, we chose a virtual reality scenario based on the Leap Motion controller: this sensor device captures the movements of the user's hand and fingers, which are reproduced on a computer screen by the proper software applications. For our experiment, we employed a sample of 10 subjects matched by age and sex and chosen among university students. The subjects took part in motor imagery training and immersive affordance condition (a virtual training with Leap Motion and a haptic training with real objects). After each training sessions the subject performed a recognition task, in order to investigate event-related potential (ERP) components. The results revealed significant differences in the attentional components during the Leap Motion training. During Leap Motion session, latencies increased in the occipital lobes, which are entrusted to visual sensory; in contrast, latencies decreased in the frontal lobe, where the brain is mainly activated for attention and action planning.

A new training approach in endoscopic percutaneous tracheostomy using a simulation model based on biological tissue.

BACKGROUND: Ciaglia et al. originally proposed the percutaneous tracheostomy in 1985 as an alternative to the surgical approach. Several variants have been developed in the years with a convincing evidence that, compared to surgical tracheostomy, the percutaneous approach is more cost-effective without compromising safety. However the procedure is not immune from complications and requires procedural skills and adequate level of expertise with a steep learning curve. In this contest, to optimize safety and efficacy of percutaneous tracheostomy in different clinical scenarios, physicians should be familiar with the different available percutaneous techniques. Traditionally, the training has been performed using manikins or animal models. However, by definition the manikin is not able to replicate the complex anatomy and does not provide a realist model for learning. METHODS: A sheep model was implemented and was tested in a simulation-based course for percutaneous dilational tracheostomy and cricothyrotomy organized by the Department of Surgical Sciences of University of Turin at the Special Educational Section of the Veterinary Sciences Department (University of Turin). RESULTS: From September 2012 to December 2014, 2 sessions of the training course were performed. Thirty-two anesthesiologists (16 men and 16 women, mean (SD) age 40.4 (SD 8.6) attended the course. A quality assessment of the course was then collected by participants. CONCLUSIONS: The biological model we implemented proved to be adequate and effective. Future studies are required to compare its efficacy with previously proposed training methods.

Ventilatory Management During Normothermic Ex Vivo Lung Perfusion: Effects on Clinical Outcomes.

BACKGROUND: During ex vivo lung perfusion (EVLP), fixed ventilator settings and monitoring of compliance are used to prevent ventilator-induced lung injury (VILI). Analysis of the airway pressure-time curve (stress index) has been proposed to assess the presence of VILI. We tested whether currently proposed ventilator settings expose lungs to VILI during EVLP and whether the stress index could identify VILI better than compliance. METHODS: Flow, volume, and airway opening pressure were collected continuously during EVLP. Durations of mechanical ventilation, intensive care unit (ICU) and hospital lengths of stay were recorded in lung recipients. RESULTS: Fourteen lungs underwent EVLP and were transplanted. In 5 lungs, 95 ± 2% of the stress index values were within the 0.95 to 1.05 range (protected); in the remaining nine lungs, 69 ± 1% of the values were greater than 1.05 and 15 ± 3% were less than 0.95 (nonprotected). There was a significant (P < 0.05) increase in cytokine concentrations after 4 hours of EVLP in the nonprotected lungs. Durations of mechanical ventilation, ICU, and hospital lengths of stay were shorter in recipients of protected than that of nonprotected lungs (P < 0.05). There was no correlation between compliance during EVLP and duration of mechanical ventilation or ICU and hospital lengths of stay in recipients, but the stress index during EVLP was significantly correlated with the duration of mechanical ventilation and with ICU and hospital lengths of stay (P < 0.05). CONCLUSIONS: This small, preliminary study shows that ventilator settings currently proposed for EVLP may expose lungs to VILI. Use of the stress index to personalize ventilator settings needs to be tested in further clinical studies.

Tracheostomy in mechanical ventilation.

Airway access for mechanical ventilation (MV) can be provided either by orotracheal intubation (OTI) or tracheostomy tube. During episodes of acute respiratory failure, patients are commonly ventilated through an orotracheal tube that represents an easy and rapid initial placement of the airway device. OTI avoids acute surgical complications such as bleeding, nerve and posterior tracheal wall injury, and late complications such as wound infection and tracheal lumen stenosis that may emerge due to tracheostomy tube placement. Tracheostomy is often considered when MV is expected to be applied for prolonged periods or for the improvement of respiratory status, as this approach provides airway protection, facilitates access for secretion removal, improves patient comfort, and promotes progression of care in and outside the intensive care unit (ICU). The aim of this review is to assess the frequency and performance of different surgical or percutaneous dilational tracheostomy and timing and safety procedures associated with the use of fiberoptic bronchoscopy and ultrasounds. Moreover, we analyzed the performance based on National European surveys to assess the current tracheostomy practice in ICUs.

Extracorporeal membrane oxygenation in adult patients with acute respiratory distress syndrome.

PURPOSE OF REVIEW: To examine the role of extracorporeal membrane oxygenation (ECMO) as potential therapeutic option for severe cases of acute respiratory distress syndrome (ARDS). RECENT FINDINGS: The use of ECMO to treat acute respiratory failure dramatically increased. Factors that may explain this increase in the use of ECMO are H1N1 pandemic influenza, results of recent clinical trials and not lastly the technological development and consequently the commercial pressure of the industry. Under these circumstances, clinicians urgently need clinical trials and formal indication, contraindication and rules for implementation to provide reproducible results. SUMMARY: Guidelines from the Extracorporeal Life Support Organization still indicate ECMO for acute severe pulmonary failure potentially reversible and unresponsive to conventional management. The new definition of ARDS (Berlin definition) addresses clinicians to the best treatment options in respect of the severity of illness and allocates ECMO as a potential therapeutic option for patients with severe ARDS and a P/F ratio lower than 100 and proposed that the indication of ECMO may be shifted from the treatment of choice for refractory hypoxemia to the treatment of choice to minimize ventilator-induced lung injury.

Accuracy of plateau pressure and stress index to identify injurious ventilation in patients with acute respiratory distress syndrome.

BACKGROUND: Guidelines suggest a plateau pressure (PPLAT) of 30 cm H(2)O or less for patients with acute respiratory distress syndrome, but ventilation may still be injurious despite adhering to this guideline. The shape of the curve plotting airway pressure versus time (STRESS INDEX) may identify injurious ventilation. The authors assessed accuracy of PPLAT and STRESS INDEX to identify morphological indexes of injurious ventilation. METHODS: Indexes of lung aeration (computerized tomography) associated with injurious ventilation were used as a "reference standard." Threshold values of PPLAT and STRESS INDEX were determined assessing the receiver-operating characteristics ("training set," N = 30). Accuracy of these values was assessed in a second group of patients ("validation set," N = 20). PPLAT and STRESS INDEX were partitioned between respiratory system (Pplat,Rs and STRESS INDEX,RS) and lung (PPLAT,L and STRESS INDEX,L; esophageal pressure; "physiological set," N = 50). RESULTS: Sensitivity and specificity of PPLAT of greater than 30 cm H(2)O were 0.06 (95% CI, 0.002-0.30) and 1.0 (95% CI, 0.87-1.00). PPLAT of greater than 25 cm H(2)O and a STRESS INDEX of greater than 1.05 best identified morphological markers of injurious ventilation. Sensitivity and specificity of these values were 0.75 (95% CI, 0.35-0.97) and 0.75 (95% CI, 0.43-0.95) for PPLAT greater than 25 cm H(2)O versus 0.88 (95% CI, 0.47-1.00) and 0.50 (95% CI, 0.21-0.79) for STRESS INDEX greater than 1.05. Pplat,Rs did not correlate with PPLAT,L (R(2) = 0.0099); STRESS INDEX,RS and STRESS INDEX,L were correlated (R(2) = 0.762). CONCLUSIONS: The best threshold values for discriminating morphological indexes associated with injurious ventilation were Pplat,Rs greater than 25 cm H(2)O and STRESS INDEX,RS greater than 1.05. Although a substantial discrepancy between Pplat,Rs and PPLAT,L occurs, STRESS INDEX,RS reflects STRESS INDEX,L.

Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a randomized controlled trial.

CONTEXT: Tracheotomy is used to replace endotracheal intubation in patients requiring prolonged ventilation; however, there is considerable variability in the time considered optimal for performing tracheotomy. This is of clinical importance because timing is a key criterion for performing a tracheotomy and patients who receive one require a large amount of health care resources. OBJECTIVE: To determine the effectiveness of early tracheotomy (after 6-8 days of laryngeal intubation) compared with late tracheotomy (after 13-15 days of laryngeal intubation) in reducing the incidence of pneumonia and increasing the number of ventilator-free and intensive care unit (ICU)-free days. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial performed in 12 Italian ICUs from June 2004 to June 2008 of 600 adult patients enrolled without lung infection, who had been ventilated for 24 hours, had a Simplified Acute Physiology Score II between 35 and 65, and had a sequential organ failure assessment score of 5 or greater. INTERVENTION: Patients who had worsening of respiratory conditions, unchanged or worse sequential organ failure assessment score, and no pneumonia 48 hours after inclusion were randomized to early tracheotomy (n = 209; 145 received tracheotomy) or late tracheotomy (n = 210; 119 received tracheotomy). MAIN OUTCOME MEASURES: The primary endpoint was incidence of ventilator-associated pneumonia; secondary endpoints during the 28 days immediately following randomization were number of ventilator-free days, number of ICU-free days, and number of patients in each group who were still alive. RESULTS: Ventilator-associated pneumonia was observed in 30 patients in the early tracheotomy group (14%; 95% confidence interval [CI], 10%-19%) and in 44 patients in the late tracheotomy group (21%; 95% CI, 15%-26%) (P = .07). During the 28 days immediately following randomization, the hazard ratio of developing ventilator-associated pneumonia was 0.66 (95% CI, 0.42-1.04), remaining connected to the ventilator was 0.70 (95% CI, 0.56-0.87), remaining in the ICU was 0.73 (95% CI, 0.55-0.97), and dying was 0.80 (95% CI, 0.56-1.15). CONCLUSION: Among mechanically ventilated adult ICU patients, early tracheotomy compared with late tracheotomy did not result in statistically significant improvement in incidence of ventilator-associated pneumonia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00262431.

Extracorporeal CO2 removal.

The extracorporeal carbon dioxide removal (ECCO(2)R) concept, used as an integrated tool with conventional ventilation, plays a role in adjusting respiratory acidosis consequent to tidal volume (Vt) reduction in a protective ventilation setting. This concept arises from the extracorporeal membrane oxygenation (ECMO) experience. Kolobow and Gattinoni were the first to introduce extracorporeal support, with the intent to separate carbon dioxide removal from oxygen uptake; they hypothesized that to allow the lung to 'rest' oxygenation via mechanical ventilation could be dissociated from decarboxylation via extracorporeal carbon dioxide removal. Carbon dioxide is removed by a pump-driven modified ECMO machine with veno-venous bypass, while oxygenation is accomplished by high levels of positive end-expiratory pressure, with a respiratory rate of 3-5 breaths/min. The focus was that, in case of acute respiratory failure, CO(2) extraction facilitates a reduction in ventilatory support and oxygenation is maintained by simple diffusion across the patient's alveoli, called 'apneic oxygenation'. Concerns have been raised regarding the standard use of extracorporeal support because of the high incidence of serious complications: hemorrhage; hemolysis, and neurological impairments. Due to the negative results of a clinical trial, the extensive resources required and the high incidence of side effects, low frequency positive pressure ventilation ECCO(2)R was restricted to a 'rescue' therapy for the most severe case of acute respiratory distress syndrome (ARDS). Technological improvement led to the implementation of two different CO(2) removal approaches: the iLA called 'pumpless arteriovenous ECMO' and the veno-venous ECCO(2)R. They enable consideration of extracorporeal support as something more than mere rescue therapy; both of them are indicated in more protective ventilation settings in case of severe ARDS, and as a support to the spontaneous breathing/lung function in bridge to lung transplant. The future development of more and more efficient devices capable of removing a substantial amount of carbon dioxide production (30-100%) with blood flows of 250-500 ml/min is foreseeable. Moreover, in the future ARDS management should include a minimally invasive ECCO(2)R circuit associated with noninvasive ventilation. This would embody the modern mechanical ventilation philosophy: avoid tracheal tubes; minimize sedation, and prevent ventilator-induced acute lung injury and nosocomial infections.