Thermodynamic Stability Implies Causality.

The stability conditions of a relativistic hydrodynamic theory can be derived directly from the requirement that the entropy should be maximized in equilibrium. Here, we use a simple geometrical argument to prove that, if the hydrodynamic theory is stable according to this entropic criterion, then localized perturbations to the equilibrium state cannot propagate outside their future light cone. In other words, within relativistic hydrodynamics, acausal theories must be thermodynamically unstable, at least close to equilibrium. We show that the physical origin of this deep connection between stability and causality lies in the relationship between entropy and information. Our result may be interpreted as an "equilibrium conservation theorem," which generalizes the Hawking-Ellis vacuum conservation theorem to finite temperature and chemical potential.

Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia.

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG.

PURPOSE: Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR. METHODS: Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3 months, was measured at birth. RESULTS: 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]. CONCLUSION: Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied. TRIAL REGISTRATION: Clinical trial registration: NCT03389178.

The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.

AIMS: Paediatric low-grade gliomas (pLGGs) are a heterogeneous group of brain tumours associated with a high overall survival: however, they are prone to recur and supratentorial lesions are difficult to resect, being associated with high percentage of disease recurrence. Our aim was to shed light on the biology of pLGGs. METHODS: We performed microRNA profiling on 45 fresh-frozen grade I tumour samples of various histological classes, resected from patients aged ≤16 years. We identified 93 microRNAs specifically dysregulated in tumours as compared to non-neoplastic brain tissue. Pathway analysis of the microRNAs signature revealed PI3K/AKT signalling as one of the centrally enriched oncogenic signalling. To date, activation of the PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been fully investigated yet. RESULTS: One of the most markedly down-regulated microRNAs in our supratentorial pLGGs cohort was miR-139-5p, whose targets include the gene encoding the PI3K's (phosphatidylinositol 3-kinase) catalytic unit, PIK3CA. We investigated the role of miR-139-5p in regulating PI3K/AKT signalling by the use of human cell cultures derived from supratentorial pLGGs. MiR-139-5p overexpression inhibited pLGG cell proliferation and decreased the phosphorylation of PI3K target AKT and phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of PI3K/AKT/mTORC1 signalling activation. The effect of miR-139-5p was mediated by PI3K inhibition, as suggested by the decrease in proliferation and phosphorylation of AKT and p70 S6K after treatment with the direct PI3K inhibitor LY294002. CONCLUSIONS: These findings provide the first evidence that down-regulation of miR-139-5p in supratentorial pLGG drives cell proliferation by derepressing PI3K/AKT signalling.

Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.

BACKGROUND: Driving pressure (ΔP) represents tidal volume normalised to respiratory system compliance (CRS) and is a novel parameter to target ventilator settings. We conducted a study to determine whether CRS and ΔP reflect aerated lung volume and dynamic strain during general anaesthesia. METHODS: Twenty non-obese patients undergoing open abdominal surgery received three PEEP levels (2, 7, or 12 cm H2O) in random order with constant tidal volume ventilation. Respiratory mechanics, lung volumes, and alveolar recruitment were measured to assess end-expiratory aerated volume, which was compared with the patient's individual predicted functional residual capacity in supine position (FRCp). RESULTS: CRS was linearly related to aerated volume and ΔP to dynamic strain at PEEP of 2 cm H2O (intraoperative FRC) (r=0.72 and r=0.73, both P<0.001). These relationships were maintained with higher PEEP only when aerated volume did not overcome FRCp (r=0.73, P<0.001; r=0.54, P=0.004), with 100 ml lung volume increases accompanied by 1.8 ml cm H2O-1 (95% confidence interval [1.1-2.5]) increases in CRS. When aerated volume was greater or equal to FRCp (35% of patients at PEEP 2 cm H2O, 55% at PEEP 7 cm H2O, and 75% at PEEP 12 cm H2O), CRS and ΔP were independent from aerated volume and dynamic strain, with CRS weakly but significantly inversely related to alveolar dead space fraction (r=-0.47, P=0.001). PEEP-induced alveolar recruitment yielded higher CRS and reduced ΔP only at aerated volumes below FRCp (P=0.015 and 0.008, respectively). CONCLUSIONS: During general anaesthesia, respiratory system compliance and driving pressure reflect aerated lung volume and dynamic strain, respectively, only if aerated volume does not exceed functional residual capacity in supine position, which is a frequent event when PEEP is used in this setting.

Adenomyoepithelioma of the breast: case report and literature review.

Adenomyoepithelioma are uncommon tumors. The majority of them occur in women in the fifth and sixth decades who usually present with a self-palpated, solitary breast mass or a lesion identified on mammography. We report the case of adenomyoepithelioma of the breast with malignant transformation of both myoepitheliel and epithelial components diagnosed as malignancy during the preoperative stage in a seventy-six year old woman.

Ten important articles on noninvasive ventilation in critically ill patients and insights for the future: A report of expert opinions.

BACKGROUND: Noninvasive ventilation is used worldwide in many settings. Its effectiveness has been proven for common clinical conditions in critical care such as cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbations. Since the first pioneering studies of noninvasive ventilation in critical care in the late 1980s, thousands of studies and articles have been published on this topic. Interestingly, some aspects remain controversial (e.g. its use in de-novo hypoxemic respiratory failure, role of sedation, self-induced lung injury). Moreover, the role of NIV has recently been questioned and reconsidered in light of the recent reports of new techniques such as high-flow oxygen nasal therapy. METHODS: We conducted a survey among leading experts on NIV aiming to 1) identify a selection of 10 important articles on NIV in the critical care setting 2) summarize the reasons for the selection of each study 3) offer insights on the future for both clinical application and research on NIV. RESULTS: The experts selected articles over a span of 26 years, more clustered in the last 15 years. The most voted article studied the role of NIV in acute exacerbation chronic pulmonary disease. Concerning the future of clinical applications for and research on NIV, most of the experts forecast the development of innovative new interfaces more adaptable to patients characteristics, the need for good well-designed large randomized controlled trials of NIV in acute "de novo" hypoxemic respiratory failure (including its comparison with high-flow oxygen nasal therapy) and the development of software-based NIV settings to enhance patient-ventilator synchrony. CONCLUSIONS: The selection made by the experts suggests that some applications of NIV in critical care are supported by solid data (e.g. COPD exacerbation) while others are still waiting for confirmation. Moreover, the identified insights for the future would lead to improved clinical effectiveness, new comparisons and evaluation of its role in still "lack of full evidence" clinical settings.

BRAF V600E expression and distribution in desmoplastic infantile astrocytoma/ganglioglioma.

AIMS: Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare primary neuroepithelial brain tumour typically affecting paediatric patients younger than 24 months. Knowledge about genetic alterations in DIA/DIG is limited. However, a previous study on BRAF V600E mutation in paediatric glioma revealed a BRAF mutation in one of two tested DIAs/DIGs. The limited number of cases in that study did not allow any conclusion about mutation frequency of BRAF in this tumour entity. METHODS: We collected a series of 18 DIAs/DIGs for testing BRAF V600E mutational status by BRAF V600E immunohistochemistry (clone VE1). Cases with sufficient DNA were tested for BRAF V600E mutation by pyrosequencing. RESULTS: Three out of 18 DIAs/DIGs presented with VE1 binding. A considerable proportion of BRAF V600E mutated tumour cells was detected in the cortical tumour component, whereas the pronounced leptomeningeal tumoural stroma was predominantly negative for VE1 binding. Pyrosequencing confirmed BRAF V600E mutation in two of three VE1-positive cases. CONCLUSION: BRAF V600E mutation affects a subset of DIAs/DIGs and offers new therapeutic opportunities.

Optimization of low energy sonication treatment for granular activated carbon colonizing biomass assessment.

This study is aimed at optimizing a low energy sonication (LES) treatment for granular activated carbon (GAC)-colonizing biomass detachment and determination, evaluating detachment efficiency and the effects of ultrasound exposure on bacterial cell viability. GAC samples were collected from two filters fed with groundwater. Conventional heterotrophic plate count (HPC) and fluorescence microscopy with a double staining method were used to evaluate cell viability, comparing two LES procedures, without and with periodical bulk substitution. A 20 min LES treatment, with bulk substitution after cycles of 5 min as maximum treatment time, allowed to recover 87%/100% of attached biomass, protecting detached bacteria from ultrasound damaging effects. Observed viable cell inactivation rate was 6.5/7.9% cell/min, with membrane-compromised cell damage appearing to be even higher (11.5%/13.1% cell/min). Assessing bacterial detachment and damaging ultrasound effects, fluorescence microscopy turned out to be more sensitive compared to conventional HPC. The optimized method revealed a GAC-colonizing biomass of 9.9 x 10(7) cell/gGAC for plant 1 and 8.8 x 10(7) cell/gGAC for plant 2, 2 log lower than reported in literature. The difference between the two GAC-colonizing biomasses is higher in terms of viable cells (46.3% of total cells in plant 1 GAC-colonizing biomass compared to the 33.3% in plant 2). Studying influent water contamination through multivariate statistical analyses, apossible combined toxic and genotoxic effect of chromium VI and trichloroethylene was suggested as a reason for the lower viable cell fraction observed in plant 2 GAC-colonizing population.

Do institutions matter for citizens' health status? Empirical evidence from Italy.

This paper investigates the role of institutional quality in explaining cross-regional variation in population health status in Italy. We first introduce a composite Regional Health Status Indicator summarizing life expectancy, mortality and morbidity data. Then, we study the empirical relationship between this indicator and a set of socioeconomic, health system and institutional controls at the Italian regional level over the period of 2011-2019. We find that institutional quality is a driver of population health. Furthermore, well-functioning local institutions and regions compliant with national standards in terms of public healthcare services (Essential Levels of Care) make socioeconomic context no longer relevant for population health, potentially reducing inequalities.

Development and validation of a comprehensive model to predict complications after hepatectomy.

OBJECTIVE: Despite advances in perioperative care, hepatectomy remains associated with morbidity rates of up to 40%. Currently, available nomograms for predicting severe post-hepatectomy complications do not include early postoperative data. This retrospective observational study aimed to determine whether the parameters routinely measured in patients admitted to the Intensive Care Unit (ICU) after hepatectomy could represent risk factors for severe morbidity and to propose a nomogram scoring system to predict severe postoperative complications. PATIENTS AND METHODS: 411 adult patients who underwent elective hepatectomy at a high-volume tertiary care center for hepatic surgery from December 2016 to June 2022 were enrolled. The primary outcome was the assessment of predictors of 30-day severe postoperative complications following hepatectomy, defined as Clavien-Dindo grade 3a or higher. As a secondary outcome, we aimed to develop an easy-to-use scoring system to estimate the risk of severe postoperative complications. RESULTS: Severe complications occurred in 78 patients (19%). The final model included body mass index, preoperative bilirubin level, and ICU data (i.e., pH, lactate clearance, arterial lactate concentration 12 hours after ICU admission, need for packed red blood cell transfusions, and length of stay). Notably, the latter three variables were proven to be independent predictors of the outcomes. The model showed an overall good fit (C-index=0.754, corrected Dxy=0.692). A calibration plot using bootstrap internal validity resampling confirmed the stability of the model (mean absolute error=0.017, root mean square error of approximation=0.00051). CONCLUSIONS: We developed an accurate and practical scoring system based on preoperative and early postoperative data to predict poor outcomes after hepatectomy. Further external validation on larger series could lead to the integration of such a tool in the routine clinical practice to support patients' management and early warning during ICU stay. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-Abstract-NEW-2.pdf.

Pilot randomized experimental study evaluating isopropyl alcohol and ultraviolet-C radiation in the disinfection of healthcare workers' smartphones.

BACKGROUND: Smartphones in medical settings pose infection risks due to harbouring pathogenic bacteria. AIM: This pilot study assessed the effectiveness duration of sanitization methods, focusing on 70% isopropyl alcohol wipes and ultraviolet-C (UVC) boxes, aiming to obtain preliminary data on the reduction in total bacterial load 3 h post-sanitization. METHODS: A randomized monocentric trial with two intervention arms (wipes and UVC boxes) was designed. As participants, healthcare workers from three wards at Fondazione Policlinico Universitario 'A. Gemelli' IRCCS Hospital were recruited, stratified by ward, and block randomized within each ward to control confounders. FINDINGS: Seventy-one healthcare workers, mostly nurses (62%) were included in the study. Initial bacterial load reduction was significant with both disinfection techniques, but after 3 h both methods showed increased bacterial levels, with wipes displaying potentially higher residual efficacy (P=0.056). To adequately size a trial (89% power, significance level 0.05) for assessing the residual efficacy of alcohol-impregnated wipes compared with UVC boxes at 3 h post-sanitization, 503 professionals per group were required. CONCLUSION: This study highlights the necessity for guidelines on hospital smartphone sanitization and educational initiatives for healthcare workers and patients. Further studies, adequately sized, are necessary to determine optimal sanitization intervals and assess pathogen transmission risks.

Baclofen in the treatment of persistent hiccup: a case series.

BACKGROUND: Persistent hiccup is a worrying symptom both for patients, because of reduced quality of life, and for physicians, because of frustration for unsuccessful treatments. AIM: To test baclofen administration for the treatment of persistent hiccup. METHOD: We report a series of seven patients affected by persistent hiccup successfully treated with baclofen. RESULTS: Hiccup stopped in all patients after a single administration of the drug. CONCLUSIONS: Baclofen is a GABA(B) receptor agonist. It is conceivable that the reduction of dopamine release by GABA(B) receptor stimulation is able to interrupt hiccup's reflex arc.

Peracetic acid for secondary effluent disinfection: a comprehensive performance assessment.

The paper is a review of previous research on secondary effluent disinfection by peracetic acid (PAA) integrated with new data about the effect of a preliminary flash-mixing step. The process was studied at bench and pilot scale to assess its performance for discharge in surface water and agricultural reuse (target microorganisms: Escherichia coli and faecal coliform bacteria). The purposes of the research were: (1) determining PAA decay and disinfection kinetics as a function of operating parameters, (2) evaluating PAA suitability as a disinfectant, (3) assessing long-term disinfection efficiency, (4) investigating disinfected effluent biological toxicity on some aquatic indicator organisms (Vibrio fischeri, Daphnia magna and Selenastrum capricornutum), (5) comparing PAA with conventional disinfectants (sodium hypochlorite, UV irradiation). PAA disinfection was capable of complying with Italian regulations on reuse (10 CFU/100 mL for E. coli) and was competitive with benchmarks. No regrowth phenomena were observed, as long as needed for agricultural reuse (29 h after disinfection), even at negligible concentrations of residual disinfectant. The toxic effect of PAA on the aquatic environment was due to the residual disinfectant in the water, rather than to chemical modification of the effluent.

Searching for a compromise between ecological quality targets, and social and ecosystem costs for heavily modified water bodies (HMWBs): the Lambro-Seveso-Olona system case study.

The Lambro-Seveso-Olona (L-S-O) system derives from the human regulation of the natural hydrology of the territory around Milan city area. The average population density in the L-S-O area is among the highest in Italy and Europe. Industry is also highly developed in this basin: chemical, textile, paper, pulp and food industries being the most important ones. Although, at present, the L-S-O system no longer receives the untreated wastewaters of the Milan urban area, treated wastewaters constitute about half of the streamflow. Biotic communities in this river have a long history of poor quality status, having suffered great damage due to domestic and industrial discharges. Recently, new chemical quality standards for macropollutants have been set by the Italian legislation as support for the good ecological status according to the Water Framework Directive (WFD). This new index is very restrictive, and it makes it extremely challenging to achieve the water quality objectives for the L-S-O system. The aim of this study is to analyse through a modelling exercise the restoration possibilities of the L-S-O system, investigating both the source apportionment of the macropollutants, the discharge limits that should be set to achieve the good quality status and their corresponding cost.

The future of intensive care medicine.

Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved.

Comparative bench study evaluation of a modified snorkeling mask used during COVID-19 pandemic and standard interfaces for non-invasive ventilation.

PURPOSE: The aim of this bench study is to compare the standard NIV and nCPAP devices (Helmet, H; Full face mask, FFM) with a modified full face snorkeling mask used during COVID-19 pandemic. METHODS: A mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort, were determined relative to the preset CPAP level. NIV was applied in Pressure Support Mode at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study, we measured the variables defining patient-ventilator interaction and performance. RESULTS: During nCPAP, the tested interfaces did not show significant differences in terms of ∆Pawi and ∆Pawe. During NIV, the snorkeling mask demonstrated a better patient-ventilator interaction compared to FFM, as shown by significantly shorter Pressurization Time and Expiratory Trigger Delay (p < 0.01), but no significant differences were found in terms of Inspiratory Trigger Delay and Time of Synchrony between the interfaces tested. At RR 20sim, the snorkeling mask presented the lower ΔPtrigger (p < 0.01), moreover during all the conditions tested the snorkeling mask showed the longer Pressure Time Product at 200, 300, and 500 ms compared to FFM (p < 0.01). A major limitation of snorkeling mask is that during NIV with this interface it is possible to reach maximum 18 cmH2O of peak inspiratory pressure. CONCLUSIONS: The modified snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergencies.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

MBR fouling control and permeate quality enhancement by polyaluminium chloride dosage: a case study.

Scope of this study was to evaluate the effectiveness of a metal salt (polyaluminium chloride, PACl) dosage into a pilot-scale MBR (membrane bioreactor) in terms of fouling control and permeate quality enhancement, especially with reference to specific textile macro-pollutants (dyes and surfactants). The pilot plant was fed with a mixed domestic-textile wastewater (textile wastewater accounted for 65% of total flow and for 70% of total chemical oxygen demand, COD, load) and operated for 7.5 months without flux enhancers (step 1) and 3 months with the addition of PACl (step 2). The optimum dose was defined performing a jar-test campaign between step 1 and step 2 (12.5 mg gMLSS(-1) that corresponds to 0.4 g d(-1)). The addition of PACl resulted in a significant decrease of the filtration resistance due to cake layer formation (R(c), -65.4%) and of the irreversible fouling rate, evaluated as the average variation per unit time of the filtration resistance due to foulants adsorption on membrane pore wall (FR, -45.3%). As for permeate quality, removal rates related to total phosphorus and textile macro-parameters such as colour and anionic surfactants, increased by +64, +16 and +7%, respectively. No significant effect was observed on COD, non-ionic surfactants and nitrogen compounds removal.