Microscopic dynamics of gas molecules confined in porous channel-like ice structure.

In the rich ice polymorphism landscape, ice XVII, metastable at ambient pressure and at temperatures below 130 K, is surely one of the most interesting from both fundamental and technological perspectives due to its porosity, i.e., its capability to repeatedly absorb and desorb molecular hydrogen by dosing the gas at pressures even below the ambient one. Here, owing to this exceptional key feature, we investigate the roto-vibrational dynamics of the H2 molecules trapped in the fully deuterated ice XVII structure. Making use of the high-resolution and brilliance of the TOSCA neutron vibrational spectrometer, combined with high-resolution Raman data, we are able to efficiently distinguish the center-of-mass translational bands from the rotational ones and to study them as a function of the guest filling of the ice structure, unraveling a peculiar behavior for the confined particle in a low-dimensional system. Moreover, we also report the study of the microscopic dynamics of confined nitrogen and oxygen, which are the most abundant molecular species in the atmosphere and are of paramount interest for technological applications. Finally, we show that the ice XVII porosity is a unique feature, especially in the low pressure regime, within the emptied-hydrate phases discovered to date.

Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock.

BACKGROUND: Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. METHODS: Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters. RESULTS: 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes. CONCLUSIONS: Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result. TRIAL REGISTRATION: NCT02750163.

Microvascular dysfunction in pediatric patients with SARS-COV-2 pneumonia: report of three severe cases.

The coronavirus 19 (COVID-19) pandemic has affected hundreds of millions of people worldwide: in most of cases children and young people developed asymptomatic or pauci-symptomatic clinical pictures. However authors have showed that there are some categories of childhood more vulnerable to COVID-19 infection such as newborns or children with comorbidities. We report for the first time to the best of our knowledge about microvascular dysfunction in three pediatric clinical cases who developed COVID-19 infections with need of pediatric critical care. We found that sublingual microcirculation is altered in children with severe COVID-19 infection. Our findings confirmed most of data already observed by other authors in adult population affected by severe COVID-19 infection, but with distinct characteristics than microcirculation alterations previous observed in a clinical case of MIS-C. However we cannot establish direct correlation between microcirculation analysis and clinical or laboratory parameters in our series, by our experience we have found that sublingual microcirculation analysis allow clinicians to report directly about microcirculation dysfunction in COVID-19 patients and it could be a valuable bedside technique to monitor thrombosis complication in this population.

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study.

PURPOSE: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. METHODS: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. RESULTS: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09). CONCLUSION: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. TRIAL REGISTRATION: Clinical trial registration number: NCT03354793.

Tocilizumab in COVID-19 interstitial pneumonia.

BACKGROUND: Published reports on tocilizumab in COVID-19 pneumonitis show conflicting results due to weak designs or heterogeneity in critical methodological issues. METHODS: This open-label trial, structured according to Simon's optimal design, aims to identify factors predicting which patients could benefit from anti-IL6 strategies and to enhance the design of unequivocal and reliable future randomized trials. A total of 46 patients with COVID-19 pneumonia needing of oxygen therapy to maintain SO2 > 93% and with recent worsening of lung function received a single infusion of tocilizumab. Clinical and biological markers were measured to test their predictive values. Primary end point was early and sustained clinical response. RESULTS: Twenty-one patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 h after tocilizumab infusion (P = 0.049) and higher baseline values of PaO2/FiO2 (P = 0.008) predicted a favourable response. CONCLUSIONS: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in patients selected according to our inclusion criteria warrants investigations in randomized trials.

The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice.

Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non-technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.

Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: Juvenile- or adult-onset forms of severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting as complicated hereditary spastic paraplegia have rarely been described. METHODS: Two siblings with mental retardation developed a progressive spastic paraparesis in their late teens. Their diagnostic assessment included extensive neurophysiologic, neuroimaging and metabolic studies. RESULTS: Brain magnetic resonance imaging showed occipital white matter alterations, and electromyography documented a mixed polyneuropathy. Severe hyperhomocisteinemia (>150 µmol/L) associated with the characteristic amino acid profile suggested a diagnosis of severe MTHFR deficiency, confirmed by MTHFR direct sequencing. Treatment with betaine and vitamins benefitted patients' symptoms and diagnostic features. CONCLUSIONS: Severe MTHFR deficiency can be a rare, treatable cause of autosomal recessive complicated hereditary spastic paraplegia. Its screening should be part of the diagnostic flowchart for these disorders.

Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study.

BACKGROUND: Acetaminophen (ACT) has been studied in septic patients with detectable plasmatic levels of cell-free hemoglobin (Hb), where it demonstrated to inhibit the hemoprotein-mediated lipid peroxidation and oxidative injury, with a potential of beneficial effect on the endothelium. On the basis of this background, the aim of this study was to evaluate the sublingual microcirculation and the peripheral tissue perfusion before-and-after administration of ACT on clinical judgment in a cohort of febrile septic and septic shock patients. METHODS: Prospective observational study. 50 adult septic and septic shocks treated with ACT for pyrexia, where the sublingual microcirculation and the peripheral tissue perfusion with Near Infrared Spectroscopy (NIRS) and vascular occlusion test (VOT) were evaluated before ACT (t0), after 30 min (t1) and after 2 h (t2). Cell-free Hb and the markers of oxidative stress and endothelial damage were measured at t0 and t2. RESULTS: The study showed a significant increase of the density of the perfused small and total vessels of the sublingual microcirculation 30 min after the infusion of ACT; it also showed an increase of the Microvascular Flow Index (MFI) and a decrease in the heterogeneity of the flow. At a peripheral muscular level, we found an acceleration in the reperfusion curve after VOT at t1, expression of a higher reactivity of the microvasculature. CONCLUSIONS: ACT infusion did not show a clear correlation with cell-free Hb; however, it exhibited protective effect toward the microcirculation that was evident in particular in septic patients. This correlation merits further exploration.

Personality traits and behavioural and psychological symptoms in patients with mild cognitive impairment.

BACKGROUND AND AIMS: Both personality changes and behavioural and psychological symptoms (BPS) may be associated with mild cognitive impairment (MCI) in later life and help identify incipient dementia. We wished to investigate the links between personality and BPS in MCI. METHOD: We studied premorbid personality traits as estimated 5 years back and their changes in 83 control subjects and 52 MCI patients using the revised NEO Personality Inventory for the Five-Factor Model completed by a proxy. Information on BPS was obtained using the Neuropsychiatric Inventory (NPI). Analyses were controlled for current depression and anxiety. RESULTS: Premorbid neuroticism and openness to experience were associated with the total NPI score. The changes in neuroticism, extraversion, openness to experiences, and conscientiousness were associated with apathy and affective symptoms. CONCLUSIONS: Personality changes and BPS occur in MCI. The occurrence of affective BPS and apathy is associated with both premorbid personality traits and their changes.

The evolution of personality in patients with mild cognitive impairment.

AIMS: To describe personality traits and their changes in mild cognitive impairment (MCI) and control subjects. METHODS: Sixty-three MCI and 90 control subjects were asked to describe their current personality traits by the Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close relative retrospectively assessed these descriptions both as to the previous and current personality traits, using the Revised NEO Personality Inventory, Form R (NEO-PI-R). RESULTS: Self-assessed MCI subjects reported significantly lower scores in the openness dimension than control subjects [F(1, 150) = 9.84, p = 0.002, ηp(2) = 0.06]. In current observer ratings, MCI subjects had higher scores on neuroticism [F(1, 137) = 7.55, p = 0.007, ηp(2) = 0.05] and lower ones on extraversion [F(1, 137) = 6.40, p = 0.013, ηp(2) = 0.04], openness [F(1, 137) = 9.93, p = 0.002, ηp(2) = 0.07], agreeableness [F(1, 137) = 10.18, p = 0.002, ηp(2) = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001, ηp(2) = 0.16]. Previous personality traits discriminated the groups as previous openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p = 0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were negatively related to MCI group membership. In MCI subjects, conscientiousness [F(1, 137) = 19.20, p < 0.001, ηp(2) = 0.12] and extraversion [F(1, 137) = 22.27, p < 0.001, ηp(2) = 0.14] decreased between previous and current evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, ηp(2) = 0.14], whereas no significant change was found in control subjects. CONCLUSIONS: MCI subjects undergo significant personality changes. Thus, personality assessment may aid the early detection of dementia.

Motorized spiral enteroscopy: effectiveness when used for new indications.

Background and study aims: Motorized spiral enteroscopy is proven to be effective in antegrade and retrograde enteroscopy. Nevertheless, little is known about its use in less common indications. The aim of this study was to identify new indications for the motorized spiral enteroscope. Methods: Monocentric retrospective analysis of 115 patients who underwent enteroscopy using PSF-1 motorized spiral enteroscope between January 2020 and December 2022. Results: A total of 115 patients underwent PSF-1 enteroscopy. 44 (38%) were antegrade procedures and 24 (21%) were retrograde procedures in patients with normal gastrointestinal anatomy with conventional enteroscopy indications. The remaining 47 (41%) patients underwent PSF-1 procedures for secondary less conventional indications: n=25 (22%) enteroscopy-assisted ERCP, n=8 (7%) endoscopy of the excluded stomach after Roux-en-Y gastric bypass, n=7 (6%) retrograde enteroscopy after previous incomplete conventional colonoscopy and n=7 (6%) antegrade panenteroscopy of the entire small bowel. In this group of secondary indications, technical success rate was significantly lower (72.5%) as compared to technical success rates in the conventional groups (98-100%, p<0.001 Chi-square). Minor adverse events occurred in 17/115 patients (15%), all treated conservatively (AGREE I and II). Conclusion: This study demonstrates the capabilities of PSF-1 motorized spiral enteroscope for secondary indications. PSF-1 is useful to complete colonoscopy in case of long redundant colon, to reach the excluded stomach after Roux-en-Y gastric bypass, to perform unidirectional pan-enteroscopy and to perform ERCP in patients with surgically altered anatomy. However, technical success rates are lower as compared to conventional antegrade and retrograde enteroscopy procedures, with only minor adverse events.

Bridging supply and demand: relationship between cocaine seizures and prevalence estimates of consumption.

OBJECTIVES: Drug supply and demand indicators have mainly been analysed without triangulating information on environmental drug availability and consumption. This study proposes an approach to analyse the prevalence of illicit drug consumption together with indirect indicators of drug supply. STUDY DESIGN: Ecological study correlating cocaine seizure data and consumption prevalence estimates at local level, using Italian provinces as the unit of analysis. METHODS: The amount of cocaine seized in proportion to the number of potential consumers was computed at Italian provincial level from the 2005 database of the Italian Central Directorate for Anti-Drug Services. Indicators of consumption prevalence, at provincial level, in 15-16-year-old students from the 2005 European School Survey Project on Alcohol and Other Drugs (ESPAD) and 15-54-year-old respondents from the 2005 Italian Population Survey on Alcohol and Drugs (IPSAD) were correlated with the population-adjusted amount of total seizures and seizures of different sizes. ESPAD data were also regressed on seizure data after controlling for the prediction accrued by socio-economic variables that might cause covariation of seizure and consumption prevalence data. Regression-predicted prevalence values were computed and correlated with the ESPAD prevalence data for the following year. RESULTS: There was a weak general correlation between the population-adjusted total seizure and IPSAD prevalence indicators, but not ESPAD prevalence indicators. In contrast, ESPAD data were more strongly correlated with small seizures. The regression model yielded significant variance in prevalence data (18% and 23% in small and large provinces, respectively) explained by small seizures, and this remained after removing the percentage of variance explained by socio-economic factors and (particularly) education level. A moderate correlation was found between seizure-based predicted values of consumption prevalence and ESPAD values for the following year. CONCLUSIONS: Associating prevalence estimates in adolescents and cocaine seizure data at local level, after 'purifying' the data from trafficking- and wholesale-related large seizures, may represent a starting point for a geo-referenced, seizure-based analysis of initiation into cocaine consumption. This approach may support the collaboration between enforcement and health systems, helping to establish empirical regularities to be translated into useful information for local planners of drug prevention policies in areas at greater risk of increasing incidence.

Open incisional hernia repair under local anaesthesia.

BACKGROUND: The Authors give an accurate description of a method of incisional hernia repair with an open technique, under local anaesthesia. The aim of this work was to show the feasibility and safety of an open preperitoneal mesh technique, as well as giving a description of technical details and the results of incisional hernia repair under local anaesthesia. METHODS: Between January 1994 and February 2008, 129 patients underwent an open mesh surgical procedure for incisional hernia. Using some simple selection criteria: maximal diameter of the hernia orifice not greater than 10 cm, the reducibility of the hernia sack, the absence of bowel obstructive symptoms, 71 patients (55.03%) were selected to be submitted to a local anaesthesia procedure, performing an open mesh repair. RESULTS: The median operative time was 101 min. The intra-operative measurement of the hernia defect showed that: in 24 patients (33.8%) it was < 3 cm, in 37 patients (52.2%) up to 10 cm and in ten patients (14%) > 10 cm. There were only two conversions to general anaesthesia (2.8%). Among the other 69 patients only four patients (5.7%) showed transient intra-operative bradycardia. All the other 69 patients (97.2%) had immediate postoperative deambulation. Forty-four of them (63.4%) were discharged within 24 h. During follow-up (12-168 months) only two recurrences (2.8%) were registered. CONCLUSIONS: This experience clearly shows that local anaesthesia for incisional hernia repair with a open preperitoneal mesh technique is feasible, safe, and effective, having a low intra-operative risk, being cost-effective and showing very good long-term results.