Reproducible determination of transpulmonary pressures.

Oesophageal pressures, as measured in an oesophageal balloon catheter, are a validated substitute for pleural pressures. Transpulmonary pressures, indispensable to improve our understanding of ventilatory physiology, are therefore typically calculated as the difference between airway and oesophageal pressures. The oesophageal pressure signal, however, features a superimposed oscillation due to cardiac motion, not representative for pleural pressure. Additionally, oesophageal contractions or surgical manipulation can alter the signal. In practice, transpulmonary pressures are therefore manually determined from the pressure-time graphic by visual inspection of the waves and averaging a limited number of samples. We suggest an approach to extract the end-expiratory transpulmonary pressure from the raw monitoring data.•Our approach reproducibly determines end-expiratory transpulmonary pressures at a given level of set positive end-expiratory pressure at the ventilator.•Our approach ignores surgical disturbance and cardiac oscillations in the oesophageal pressure signal.

Two Cases of Post-Traumatic Mucormycosis due to Mucor circinelloides: Salvage Therapy with a Combination of Adjunctive Therapies.

Mucormycosis is a rare, emerging angioinvasive infection caused by ubiquitous filamentous fungi. In recent decades, an increase in cutaneous or post-traumatic mucormycosis has been reported. We describe two cases of post-traumatic wound infections with Mucor circinelloides, a mucor species only rarely reported as a cause of post-traumatic mucormycosis. Often considered lethal, management required a combination of medical and surgical therapies to achieve a favorable outcome in both cases.

Bilateral adrenal haemorrhage after a high energetic trauma: a case report and review of current literature.

Most adrenal injuries are asymptomatic. In traumatic events, adrenal haemorrhage is very likely to be accompanied by injuries to other organs. Isolated adrenal injury after trauma is very rare and mostly unilateral. We report a case of a 44-year-old male who suffered a major traffic accident with multiple trauma, including a bilateral adrenal haemorrhage. This caused a primary adrenal insufficiency, as proven with a cortisol stimulation test with synthetic corticotrophin. Bilateral adrenal haemorrhage is a very rare but potentially fatal disorder and should not be missed. This case illustrates that early diagnosis and prompt treatment with hydrocortisone may contribute to a beneficial outcome.

Remarkable geographical variations between India and Europe in carriage of the staphylococcal surface protein-encoding sasX/sesI and in the population structure of methicillin-resistant Staphylococcus aureus belonging to clonal complex 8.

OBJECTIVES: sasX is a colonization-virulence factor that potentially underlies the success of methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 239 in Asia. We aimed to study the spread of sasX and the population structure of MRSA in two geographically distinct regions, Europe and India. METHODS: MRSA (n = 128) from screening and clinical samples from tertiary care patients in 12 European countries (n = 119), and from India (n = 9) were multilocus-sequence-typed and screened for sasX and its carrier φSPß-like prophage by PCR. Whole genome sequencing was performed on sasX-harbouring strains from India (n = 5) and Europe (n = 2) and on a selection non-harbouring sasX (n = 36) (2 × 150 bp, Miseq, Illumina). Reads were mapped to the ST239 reference strain, TW20. RESULTS: sasX and sesI, a sasX homologue native to Staphylococcus epidermidis, were detected in five of the nine Indian MRSA belonging to ST239 and to other sequence types of CC8. In contrast, sasX was restricted to two ST239 strains in Europe. The intact sasX and sesI carrier φSPß-like prophages were ∼80 kb and ∼118 kb, and integrated in the yeeE gene. We identified 'novel' ST239 clades in India and Serbia that showed significant differences in base substitution frequencies (0.130 and 0.007, respectively, Tamura-Nei model) (p <0.05). CONCLUSIONS: Our data highlight dissemination of sasX to non-ST239 sequence types of CC8. Detection of the S. epidermidis-associated sesI in MRSA provided unquestionable evidence of transfer between the two species. Stark differences in evolutionary rates between the novel Indian and Serbian ST239 clades identified here might be due to inherent clade characteristics or influenced by other environmental differences such as antibiotic use.

Effect of isotonic versus hypotonic maintenance fluid therapy on urine output, fluid balance, and electrolyte homeostasis: a crossover study in fasting adult volunteers.

BACKGROUND.: Daily and globally, millions of adult hospitalized patients are exposed to maintenance i.v. fluid solutions supported by limited scientific evidence. In particular, it remains unclear whether fluid tonicity contributes to the recently established detrimental effects of fluid, sodium, and chloride overload. METHODS.: This crossover study consisted of two 48 h study periods, during which 12 fasting healthy adults were treated with a frequently prescribed solution (NaCl 0.9% in glucose 5% supplemented by 40 mmol litre -1 of potassium chloride) and a premixed hypotonic fluid (NaCl 0.32% in glucose 5% containing 26 mmol litre -1 of potassium) at a daily rate of 25 ml kg -1 of body weight. The primary end point was cumulative urine volume; fluid balance was thus calculated. We also explored the physiological mechanisms behind our findings and assessed electrolyte concentrations. RESULTS.: After 48 h, 595 ml (95% CI: 454-735) less urine was voided with isotonic fluids than hypotonic fluids ( P <0.001), or 803 ml (95% CI: 692-915) after excluding an outlier with 'exaggerated natriuresis of hypertension'. The isotonic treatment was characterized by a significant decrease in aldosterone ( P <0.001). Sodium concentrations were higher in the isotonic arm ( P <0.001), but all measurements remained within the normal range. Potassium concentrations did not differ between the two solutions ( P =0.45). Chloride concentrations were higher with the isotonic treatment ( P <0.001), even causing hyperchloraemia. CONCLUSIONS.: Even at maintenance rate, isotonic solutions caused lower urine output, characterized by decreased aldosterone concentrations indicating (unintentional) volume expansion, than hypotonic solutions and were associated with hyperchloraemia. Despite their lower sodium and potassium content, hypotonic fluids were not associated with hyponatraemia or hypokalaemia. CLINICAL TRIAL REGISTRATION.: ClinicalTrials.gov (NCT02822898) and EudraCT (2016-001846-24).

Retinal haemorrhages in a university hospital: not always abusive head injury.

Retinal haemorrhages (RH) and subdural haematomas (SDH) are frequently seen in abusive head trauma (AHT). The aim of our study is to show that they are suggestive, but not pathognomonic for AHT. We performed an observational retrospective study on children, aged 1-18 months old, admitted to the Antwerp University Hospital with RH. History, physical examination, medical course, coagulation and metabolic tests, skeletal survey, head circumference, retinal findings, cerebral imaging, and evaluation reports by social services or civil/criminal courts were collected. Twenty-nine children with RH were included. Twenty three of them were found suspect of AHT. Three children of this group showed intraparenchymal haematomas/infarctions, 5 interhemispheric blood, 6 cerebral oedema, 7 ventricle compression, and 4 papilloedema. Seven of the 16 children with diffusion-weighted MRI images showed diffuse lesions. In 2 of the 6 children not suspect for AHT, an aetiology was found. None of the 4 remaining children showed the above-mentioned abnormalities. Three of these 4 cases showed an accelerated growth of the head circumference months before presentation. The majority of the children in all groups showed 'too numerous to count' (>20) RH (12 of the 23 'suspect' children, and 4 of the 6 'non-suspect' children). Results showed no differences between the groups concerning the location, distribution, or size of the RH. Infants with RH and/or SDH are not necessarily victims of AHT. Cerebral imaging and retinal findings can help differentiate suspect from non-suspect cases. Infants with a large head circumference could be predisposed to RH or SDH.

Circulating phthalates during critical illness in children are associated with long-term attention deficit: a study of a development and a validation cohort.

PURPOSE: Environmental phthalate exposure has been associated with attention deficit disorders in children. We hypothesized that in children treated in the pediatric intensive care unit (PICU), circulating phthalates leaching from indwelling medical devices contribute to their long-term attention deficit. METHODS: Circulating plasma concentrations of di(2-ethylhexyl)phthalate (DEHP) metabolites were quantified in 100 healthy children and 449 children who had been treated in PICU and were neurocognitively tested 4 years later. In a development patient cohort (N = 228), a multivariable bootstrap study identified stable thresholds of exposure to circulating DEHP metabolites above which there was an independent association with worse neurocognitive outcome. Subsequently, in a second patient cohort (N = 221), the observed independent associations were validated. RESULTS: Plasma concentrations of DEHP metabolites, which were virtually undetectable [0.029 (0.027-0.031) µmol/l] in healthy children, were 4.41 (3.76-5.06) µmol/l in critically ill children upon PICU admission (P < 0.001). Plasma DEHP metabolite concentrations decreased rapidly but remained 18 times higher until PICU discharge (P < 0.001). After adjusting for baseline risk factors and duration of PICU stay, and further for PICU complications and treatments, exceeding the potentially harmful threshold for exposure to circulating DEHP metabolites was independently associated with the attention deficit (all P ≤ 0.008) and impaired motor coordination (all P ≤ 0.02). The association with the attention deficit was confirmed in the validation cohort (all P ≤ 0.01). This phthalate exposure effect explained half of the attention deficit in post-PICU patients. CONCLUSIONS: Iatrogenic exposure to DEHP metabolites during intensive care was independently and robustly associated with the important attention deficit observed in children 4 years after critical illness. Clinicaltrials.gov identifier: NCT00214916.

Pivotal Role for the Visceral Fat Compartment in the Release of Persistent Organic Pollutants During Weight Loss.

CONTEXT: Polychlorinated biphenyls (PCBs), are implicated as potential endocrine disruptors and obesogens. These lipophilic substances are preferentially stored in the fat compartment and released into the circulation during weight loss. OBJECTIVE: The aim of this study was to examine the contribution of abdominal adiposity, and visceral adiposity in particular, to the increase of serum PCB levels during weight loss. MATERIALS AND METHODS: Fourty-five obese women were prospectively recruited. Twenty individuals received dietary counseling and 25 underwent bariatric surgery. Anthropometric data were collected and intra-abdominal adiposity was assessed by measurement computed tomography scanning of the abdominal fat compartment, delineating the visceral and subcutaneous compartment. Serum levels of 27 PCBs were determined and the sum of all PCBs (ΣPCBs) calculated. Follow-up measurements of anthropometric data, computed tomography scanning, and PCB levels were performed after 6 months in all patients. RESULTS: In patients who lost weight, serum ΣPCB levels displayed an increase after 6 months of approximately 50%. Both correlation and regression analysis, focusing on the relative contribution of the visceral vs the subcutaneous fat compartment, suggested that the increase in ΣPCB serum levels after 6 months of weight loss was more pronounced in patients losing relatively more visceral adipose tissue. This trend could be established in the diet-treated, but not the surgery-treated subgroup. CONCLUSION: Our study suggests that the contribution of PCBs released from the visceral fat compartment might be more pronounced compared with the subcutaneous fat compartment during weight loss. These findings are present in the entire study group whereas subanalysis of the diet vs surgery groups suggested the same effect in the diet group but failed to reach statistical significance in the surgery group. This suggests a possible weight-loss method-specific effect.

Allergy to illicit drugs and narcotics.

Despite their frequent use, allergy to illicit drugs and narcotics is rarely reported in literature. We present a review of the different classes of drugs of abuse that might be involved in allergies: central nervous system (CNS) depressants (such as cannabis, opioids and kava), CNS stimulants (cocaine, amphetamines, khat and ephedra) and hallucinogens such as ketamine and nutmeg. Diagnosis of drug and narcotic allergy generally relies upon careful history taking, complemented with skin testing eventually along with quantification of sIgE. However, for various reasons, correct diagnosis of most of these drug allergies is not straightforward. For example, the native plant material applied for skin testing and sIgE antibody tests might harbour irrelevant IgE-binding structures that hamper correct diagnosis. Diagnosis might also be hampered due to uncertainties associated with the non-specific histamine releasing characteristics of some compounds and absence of validated sIgE tests. Whether the introduction of standardized allergen components and more functional tests, that is, basophil activation and degranulation assays, might be helpful to an improved diagnosis needs to be established. It is anticipated that due to the rare character of these allergies further validation is although necessary.

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study.

PURPOSE: Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. METHODS: A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. RESULTS: A total of 2,852 adult ICU patients were screened of which 1,824 (64%) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1%) and sustained coma (4.1%). CAM-ICU compliance was mean (SD) 82 ± 16% and inter-rater reliability 0.87 ± 0.17. The median delirium incidence was 22.5% (IQR 12.8-36.6%). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95% CI 0.74-0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. CONCLUSIONS: In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients.

Mechanical and electrical equipment interference provokes a misleading Neurally Adjusted Ventilatory Assist (NAVA) EAdi signal.

BACKGROUND: Neurally Adjusted Ventilatory Assist (NAVA) offers synchronized proportional pressure in accordance with the electrical activity of the diaphragm (EAdi). NAVA relies on the EAdi to trigger the respiratory cycle and then adjusts the ventilatory assist to the neural drive. The technique necessitates a catheter with bipolar microelectrodes positioned near the crural diaphragm where this signal can be captured. Capturing a reliable EAdi signal is a condition sine qua non for using NAVA as a mode of ventilation. The displayed signal represents the sum of the electrical activity of the muscle action potential of the diaphragm and is expressed in microvolts. METHODS: A technical note illustrated by a case series in the intensive care unit (ICU) of a tertiary referral hospital with experience using NAVA. RESULTS: Here, we report on three separate cases in which the use of an intra-aortic balloon catheter, a pacemaker and a heating device all resulted in a distortion of the EAdi signal, despite good positioning of the catheter. In a fourth case, we observed internal interference from leaking cardiac electrical activity due to the malpositioning of the EAdi catheter in a patient with atrial fibrillation. CONCLUSION: We illustrate that the detection and therefore interpretation of the EAdi signal during NAVA can be influenced by mechanical and electrical interference by other equipment used in the ICU or from endogenous leaking cardiac activity.

New food allergies in a European non-Mediterranean region: is Cannabis sativa to blame?

BACKGROUND: Allergy to fruit and vegetables exhibit geographic variation regarding the severity of symptoms and depending on the sensitization profile of the patient. These sensitization profiles and routes remain incompletely understood. Cannabis is a very popular drug and derived from Cannabis sativa, a plant containing lipid transfer proteins (LTP) also known as important allergens in plant and fruit allergies. In this study we sought to elucidate a potential connection between C. sativa allergy and plant food allergies. METHODS: A case-control study involving 21 patients consulting for plant food allergies. Twelve patients were cannabis allergic and 9 had a pollen or latex allergy without cannabis allergy. Testing for cannabis IgE implied measurement of specific IgE, skin testing and basophil activation tests. Allergen component analysis was performed with a microarray technique. RESULTS: Plant food allergy in patients with documented cannabis allergy had more severe reactions than patients without cannabis allergy and frequently implied fruits and vegetables that are not observed in a (birch) pollen-related food syndrome. With the exception of 1 patient with cannabis allergy, all were sensitized to nonspecific (ns)-LTP. CONCLUSION: Our data suggest that illicit cannabis abuse can result in cannabis allergy with sensitization to ns-LTP. This sensitization might result in various plant-food allergies. Additional collaborative studies in different geographical areas are needed to further elucidate on this hypothesis.

Impact of a standardized nurse observation protocol including MEWS after Intensive Care Unit discharge.

BACKGROUND: Analysis of in-hospital mortality after serious adverse events (SAE's) in our hospital showed the need for more frequent observation in medical and surgical wards. We hypothesized that the incidence of SAE's could be decreased by introducing a standard nurse observation protocol. AIM: To investigate the effect of a standard nurse observation protocol implementing the Modified Early Warning Score (MEWS) and a color graphic observation chart. METHODS: Pre- and post-intervention study by analysis of patients records for a 5-day period after Intensive Care Unit (ICU) discharge to 14 medical and surgical wards before (n=530) and after (n=509) the intervention. RESULTS: For the total study population the mean Patient Observation Frequency Per Nursing Shift (POFPNS) during the 5-day period after ICU discharge increased from .9993 (95% C.I. .9637-1.0350) in the pre-intervention period to 1.0732 (95% C.I. 1.0362-1.1101) (p=.005) in the post-intervention period. There was an increased risk of a SAE in patients with MEWS 4 or higher in the present nursing shift (HR 8.25; 95% C.I. 2.88-23.62) and the previous nursing shift (HR 12.83;95% C.I. 4.45-36.99). There was an absolute risk reduction for SAE's within 120h after ICU discharge of 2.2% (95% C.I. -0.4-4.67%) from 5.7% to 3.5%. CONCLUSION: The intervention had a positive impact on the observation frequency. MEWS had a predictive value for SAE's in patients after ICU discharge. The drop in SAE's was substantial but did not reach statistical significance.

Neuromonitoring in traumatic brain injury.

Current approaches to monitoring in severe traumatic brain injury (TBI) include a wide array of modalities, providing insight into pressure parameters, oxygenation, perfusion, electrophysiology and metabolism of the brain. The intent of "multimodality monitoring" is to obtain a better understanding of what is going on within the brain of an individual patient in order to target treatment more appropriately. In this review we highlight the current status of neuromonitoring for TBI with a specific focus on how advanced analysis and integration of these parameters may be used to implement more personalized treatment approaches. In particular, combining information from different parameters and performing dynamic testing offers the potential to better understand the pathophysiological mechanisms active in the brain of a particular patient. Rather than persisting in a standardized "one size fits all" approach to therapy or continuing down the separate tracts of goal directed therapy, we suggest to think more in terms of "individualized therapeutic strategies" more focused on the specific requirements of each patient. Given the considerable data overload in multimodality monitoring and the complexity in interpretation of signals from multiple sources, specific attention needs to be directed to data processing and user-friendly displays. Intense collaboration and interaction between clinicians, basic researchers, IT-experts, nurses and industry will be required to further advance the fields towards more personalized approaches.

Severe influenza A(H1N1)2009 infection: a single centre experience and review of the literature.

The first influenza pandemic of the 21st century started in April 2009 with an outbreak of swine origin influenza A(H1NI)2009 in Mexico and the United States. While generally a mild disease affecting mostly school-aged children and young adults, most attention went to severe cases of pneumonia in young previously healthy individuals or individuals belonging to a risk group. In this article we review the literature on the presentation and management of severe cases of influenza A(H1N1)2009 in the intensive care unit (ICU), and describe our own experience in a tertiary referral centre with ECMO facilities. Pregnant women and (bone marrow) transplant patients are two known risk groups for severe influenza described more thoroughly in this paper.These severely ill patients are characterized by respiratory failure, resulting often in the need of mechanical ventilation. As Oseltamivir resistance remains low up till now, early antiviral therapy with Oseltamivir is warranted in these cases. Despite pharmacological and ventilator management, refractory hypoxaemia is described frequently in these patients, with need for rescue therapies like nitric oxide inhalation, high frequency ventilation, and extracorporeal membrane oxygenation. The value of the use of corticosteroids is under discussion. Despite advances in management strategies, mortality and morbidity in these severe cases remains high. In the first influenza season after the pandemic, winter 2010/2011, influenza A(H1N1)2009 is the major influenza A strain in Europe, resulting in reports with increased mortality and morbidity compared to pre-pandemic seasonal influenza. "Continuing vigilance for severe influenza in patients not belonging to the classical influenza risk group might still be warranted for the upcoming influenza season".

Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome.

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.

Excessive eosinophilia as paraneoplastic syndrome in a patient with non-small-cell lung carcinoma: a case report and review of the literature.

Hypereosinophilia is a phenomenon which is associated with a broad variety of allergic, infectious, paraneoplastic and systemic diseases. Depending on the aetiology, these disorders differ in severity from self-limiting to life-threatening. Although it is well known that hypereosinophilia can occur in association with a solid tumour, exact numbers of incidence are lacking. We describe a patient with respiratory insufficiency and an elevated level of eosinophils in the peripheral blood. A diagnostic work-up revealed the presence of a disseminated non-small-cell carcinoma of the lung; an association not frequently described.

Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function.

The prevalence of diabetes mellitus is currently at epidemic proportions and it is estimated that it will increase even further over the next decades. Although genetic predisposition and lifestyle choices are commonly accepted reasons for the occurrence of type 2 diabetes, it has recently been suggested that environmental pollutants are additional risk factors for diabetes development and this review aims to give an overview of the current evidence for this. More specifically, because of the crucial role of pancreatic beta cells in the development and progression of type 2 diabetes, the present work summarises the known effects of several compounds on beta cell function with reference to mechanistic studies that have elucidated how these compounds interfere with the insulin secreting capacity of beta cells. Oestrogenic compounds, organophosphorus compounds, persistent organic pollutants and heavy metals are discussed, and a critical reflection on the relevance of the concentrations used in mechanistic studies relative to the levels found in the human population is given. It is clear that some environmental pollutants affect pancreatic beta cell function, as both epidemiological and experimental research is accumulating. This supports the need to develop a solid and structured platform to fully explore the diabetes-inducing potential of pollutants.