A 4C mortality score based dichotomic rule supports Emergency Department discharge of COVID-19 patients.

BACKGROUND: For COVID-19 patients evaluated in the Emergency Department (ED), decision on hospital admission vs. home discharge is challenging. The 4C mortality score (4CMS) is a prognostication tool integrating key demographic/clinical/biochemical data validated for COVID-19 inpatients. We sought to derive and validate a dichotomic rule based on 4CMS identifying patients with mild outcomes, suitable for safe ED discharge. METHODS: Derivation was performed in a prospective cohort of ED patients with suspected COVID-19 from two centers (April 2020). Validation was pursued in a prospective multicenter cohort of ED patients with confirmed COVID-19 from 6 centers (October 2020 to January 2021). Chest X-ray (CXR) images were independently scored. The primary composite outcome was all-cause 30-day mortality or hospital admission. Secondary outcomes were ED re-visit, oxygen therapy and ventilation. RESULTS: In a derivation cohort of 838 ED patients with suspected COVID-19, 4CMS≤8 was associated with low outpatient mortality (0.4%) and was thus selected as a feasible discharge rule. In a validation cohort of 521 COVID-19 outpatients, the mean age was 51±17 years; 97 (18.6%) patients had ≥1 CXR infiltrate. The 4CMS had an AUC of 0.82 for the primary outcome and 0.93 for mortality, outperforming other scores (CURB-65, qCSI, qSOFA, NEWS) and CXR. In 474 (91%) patients with 4CMS≤8, the mortality rate was 0.2% and the hospital admission rate was 6.8%, versus 12.8% and 36.2% for 4CMS≥9 (P<0.001). CXR did not provide additional discrimination. CONCLUSIONS: COVID-19 outpatients with 4CMS≤8 have mild outcomes and can be safely discharged from the ED. [NCT0462918].

Effects of liver ischemia-reperfusion injury on respiratory mechanics and driving pressure during orthotopic liver transplantation.

BACKGROUND: During orthotopic liver transplantation (OLT), liver graft ischemia-reperfusion injury (IRI) triggers a cytokine-mediated systemic inflammatory response, which impairs graft function and disrupts distal organ homeostasis. The objective of this prospective, observational trial was to assess the effects of IRI on lung and chest wall mechanics in the intraoperative period of patients undergoing OLT. METHODS: In 26 patients undergoing OLT, we measured elastance of the respiratory system (ERS), partitioned into lung (EL) and chest wall (ECW), hemodynamics, and fluid and blood product intake before laparotomy (T1), after portal/caval surgical clamp (T2), and immediately (T3) and, at 90 and 180 minutes post-reperfusion (T4 and T5, respectively). Interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1ß and tumor necrosis factor-α plasma concentrations were assessed at T1, T4 and T5. RESULTS: EL significantly decreased from T1 to T2 (13.5±4.4 vs 9.7±4.8 cmH2O/L, P<0.05), remained stable at T3, while at T4 (12.3±4.4 cmH2O/L, P<0.05) was well above levels recorded at T2, reaching its highest value at T5 (15±3.9 cmH2O/L, P<0.05). Variations in ERS, EL, driving pressure (∆P) and trans-pulmonary pressure (∆PL) significantly correlated with changes in IL-6 and MCP-1 plasma concentrations, but not with changes in wedge pressure, fluid amounts, and red blood cells and platelets administered. No correlation was found between changes in cytokine concentrations and ECW. CONCLUSIONS: We found that EL, ECW, ∆P and ∆PL underwent significant variations during the OLT procedure. Further, we documented a significant association between the respiratory mechanics changes and the inflammatory response following liver graft reperfusion.

An anatomical and histological study of the equine proximal manica flexoria.

OBJECTIVES: The main aim was to describe the gross and histological appearance of the equine manica flexoria and to identify any differences between the forelimbs and hindlimbs. An additional aim was to relate the findings to diagnostic and surgical anatomy of the manica flexoria. METHODS: Measurements of the manica flexoria were made on cadaveric limbs from horses free from pathology within the digital flexor tendon sheath. Histological sections, stained with haematoxylin and eosin and alcian- periodic acid schiff, were evaluated based on three micro-anatomical zones from dorsal to palmar or plantar. The prevalent tenocyte morphology, number, and distribution of blood vessels and nerves were described in each zone. Forelimb and hindlimb measurements were compared using a Students T-test. RESULTS: Proximally, the manica flexoria attaches to the digital flexor tendon sheath via a reflection of areolar tissue. The fibrous manica flexoria is longer in the forelimb (32.0 ± 4.2 mm) than the hindlimb (29.4 ± 3.8 mm) (p = 0.04), with the areolar portion longer in the hindlimb (22.9 ± 5.3 mm) compared to the forelimb (16.7 ± 4.3 mm) limb (p = 0.0005). Histologically, degenerate blood vessels were prevalent in the palmar/plantar regions and were associated with chondrocyte-like tenocytes, indicative of fibrocartilagenous metaplasia. CLINICAL SIGNIFICANCE: The study has provided a detailed anatomical description of the manica flexoria relevant for interpretation of diagnostic and surgical evaluation. Fibrocartilaginous metaplasia occurs on the palmar/plantar surfaces of the manica flexoria.

Supplementation with Lactobacillus rhamnosus SP1 normalises skin expression of genes implicated in insulin signalling and improves adult acne.

Systemic supplementation with probiotics is increasingly being explored as a potential treatment strategy for skin disorders. Because both the gut-skin axis and dysregulation of insulin signalling have been implicated in the pathogenesis of adult acne, we designed the current study to evaluate the effect of supplementation with the probiotic strain Lactobacillus rhamnosus SP1 (LSP1) on skin expression of genes involved in insulin signalling and acne improvement in adult subjects. A pilot, randomised, double-blinded, placebo-controlled study was conducted with 20 adult subjects (14 females and 6 males; mean age: 33.7±3.3 years) with acne. Over a 12-week period, the probiotic group (n=10) consumed a liquid supplement containing LSP1 at a dose of 3×109 cfu/day (75 mg/day), whereas the placebo group (n=10) received a liquid lacking probiotics. Paired skin biopsies - one obtained before treatment initiation and one obtained at the end of the 12-week treatment period - were analysed for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression. The clinical criterion for efficacy was the investigator's global improvement rating on a five-point scale. Compared with baseline, the probiotic group showed a 32% (P<0.001) reduction, as well as a 65% increase (P<0.001) in IGF1 and FOXO1 gene expression in the skin, respectively. No such differences were observed in the placebo group. Patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval = 2.2-411.1, P<0.05) to be rated by physicians as improved/markedly improved (versus worsened or unchanged) compared with the placebo group. We conclude that supplementation with the probiotic strain LSP1 normalises skin expression of genes involved in insulin signalling and improves the appearance of adult acne.

Bullying behaviours among students in Pavia, Italy: prevalence and association with stress and cannabis use.

BACKGROUND: This study examined the prevalence of students' reported experiences of bullying and victimization in primary and secondary schools and their association with levels of perceived stress and cannabis use. METHODS: We consecutively enrolled 407 students attending three secondary schools in Pavia (Italy). Bullying and victimization were measured using the retrospective bullying questionnaire (RQB). The 10-item perceived stress scale (PSS-10) was used to assess the degree to which situations in life were perceived as stressful. Data on demographic characteristics and cannabis use in the previous 6 months were also collected. RESULTS: There were 328 victims (80.6%) and 221 bullies (52.1%). The results of the stepwise regression analysis with bullying as the dependent variable were significant with either male sex (R2 = 0.030, p = 0.024) or PSS-10 scores (R2 0.056, p = 0.036) in the model. With victimization as the dependent variable, only the PSS-10 scores were retained in the model as an independent predictor variable (R2 = 0.048, p<0.001). CONCLUSIONS: The results from this study indicate that the level of perceived stress has an independent association with both bullying and victimization. Further studies are needed to clarify the psychobiological links between stress, cannabis use and bullying behaviours.

Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.

Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.

A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite.

BACKGROUND: Cellulite is a common complex cosmetic problem for many post-adolescent women characterised by relief alterations of the skin surface, which give the skin an orange-peel appearance. Although genetic factors have been suggested to play a role in the development of cellulite, the genetic background of this condition remains unclear. We therefore conducted a multi-locus genetic study examining the potential associations of candidate gene variants in oestrogen receptors, endothelial function/adipose tissue hypoxia, lipid metabolism, extracellular matrix homeostasis, inflammation and adipose tissue biology, with the risk of cellulite. METHODS: Using a case-control study of 200 lean women with cellulite and 200 age- and BMI-matched controls (grade 0 according to Nurnberger-Muller scale), we examined the association of cellulite with 25 polymorphisms in 15 candidate genes. RESULTS: Two of the 25 polymorphisms were significantly associated with cellulite at the P < 0.01 level. After allowance for age, body mass index, the prevalence of contraceptive use and smoking in logistic regression analysis, the multivariable-adjusted odds ratios for cellulite were 1.19 (95% CI: 1.10-1.51; P < 0.01) for ACE rs1799752 and 0.61 (95% CI: 0.45-0.88, P < 0.01) for HIF1A rs11549465. CONCLUSIONS: This study, which demonstrates an independent role of ACE and HIF1A in predisposing to cellulite, may provide novel information on the pathophysiology of this common cosmetic problem, and offer a topic for research for novel beautification interventions.

Decreased plasma levels of soluble receptor for advanced glycation end products in mild cognitive impairment.

Growing evidence advanced the idea that the soluble form of the receptor for advanced glycation end-products (sRAGE) might serve as a risk marker for several disorders including Alzheimer disease. We found a reduced level of circulating sRAGE in patients with mild cognitive impairment (MCI). The reduction of sRAGE in MCI, as well as the anticipation of the disease in patients with the lowest sRAGE levels (

The -374T/A variant of the rage gene promoter is associated with clinical restenosis after coronary stent placement.

Upregulation of the receptor for advanced glycation end products (RAGE) may play a crucial role in neointimal formation upon vessel injury. The -374T/A variant of the RAGE gene promoter, which has been associated with an altered expression of the cell-surface receptor, could exert a protective effect toward the development of vascular disease. The aim of this study is to determine the impact of this common genetic variant in the occurrence of clinical in-stent restenosis after coronary stent implantation. The -374T/A polymorphism of the RAGE gene promoter was evaluated by PCR-RFLPs in 267 patients with coronary artery disease who underwent coronary stent implantation and a subsequent coronary angiography 6-9 months later for suspected restenosis. In-stent restenosis was assessed by means of quantitative angiography. Carriers of the -374AA genotype showed a significantly reduced risk of developing restenosis after percutaneous transluminal intervention than non-carriers. To determine whether the protective effect of the homozygous AA genotype toward clinical restenosis was independent of potential confounders, we performed multivariable logistic regression analysis. After allowance for clinical and biochemical risk factors and stent length, the AA genotype remained significantly associated with a reduced prevalence of in-stent restenosis. No relation was evident between the RAGE genotype and established cardiovascular risk factors. In conclusion, the -374AA genotype of the RAGE gene promoter could be associated with a reduced risk of in-stent restenosis after coronary stent implantation.

Markers of eosinophilic inflammation and risk prediction in patients with coronary artery disease.

BACKGROUND: The eotaxin family comprises three distinct peptides (eotaxin, eotaxin-2 and eotaxin-3) which have been implicated in eosinophilic inflammation. In vitro and clinical studies suggest that eotaxins could play a role in vascular inflammation, but no data are available on their prognostic significance in patients with angiographically documented coronary artery disease (CAD). MATERIALS AND METHODS: Baseline plasma samples were obtained from 1014 patients with documented CAD. We tested the predictive effect of markers of eosinophilic inflammation and C-reactive protein (CRP) on death from cardiovascular causes and nonfatal myocardial infarction over a 2.7-4.1-year follow-up period. RESULTS: Unexpectedly, lower eotaxin-3 concentrations were observed in patients with adverse cardiovascular events, whereas both eotaxin and eotaxin-2 showed no association with risk. After adjustment for most potential confounders, patients in the upper-quartile of eotaxin-3 levels had a 0.42 hazard-ratio (95% CI, 0.29-0.61, P < 0.001) for adverse events compared with subjects in the lower-quartile. The highest risk of future cardiovascular events was observed in subjects with combined elevation of CRP and reduction of eotaxin-3; 4.4 hazard-ratio (95% CI, 2.1-9.5, P < 0.001). Importantly, receiver-operating-characteristic curves analysis suggested a superior prognostic value of eotaxin-3 compared with CRP for predicting cardiac events in patients with CAD. CONCLUSIONS: Low levels of eotaxin-3 are an independent predictor of future adverse cardiovascular events in patients with CAD and may be useful for risk stratification.

Erectile dysfunction and angiographic extent of coronary artery disease in type II diabetic patients.

Some studies observed an association between erectile dysfunction (ED) and coronary artery disease (CAD) extent in the general population, but others did not. There are no specific studies in diabetic populations. The aim of the present study was to evaluate whether ED is correlated with the extent of angiographic CAD in a large group of type II diabetic patients. We recruited 198 consecutive type II diabetic males undergoing an elective coronary angiography to evaluate chest pain or suspected CAD. Presence and degree of ED were assessed by the International Index Erectile Function - 5 (IIEF-5) questionnaire. ED was considered present, when IIEF-5 score was < or =21. Moreover, each domain of IIEF-5 was considered. Angiographic CAD extent was expressed both by the number of vessels diseased and by the Gensini scoring system. The percentage of subjects with ED was significantly higher (45.8 versus 15.8%; P=0.0120) in patients with (n=179) than in those without (n=19) significant angiographic CAD (stenosis of the lumen > or =50%). No significant association of CAD extent with presence of ED, total IIEF-5 score and each domain of IIEF-5 was observed. Our study shows that ED was significantly more prevalent in type II diabetic males with angiographic CAD than in those with normal arteries. However, no correlation was found between the extent of angiographic CAD and the presence or the severity of ED.

Apo(a) size in ischemic stroke: relation with subtype and severity on hospital admission.

OBJECTIVE: To determine the distribution of apolipoprotein (a) (apo[a]) isoforms and their relation to the clinical severity of different ischemic stroke subtypes. METHODS: Ninety-four hospital cases with a first-ever ischemic stroke and 188 randomly selected control subjects matched for age, gender, and ethnicity were enrolled. Stroke etiology was defined according to Trial of Org 10172 in Acute Stroke Treatment criteria. NIH Stroke Scale (NIHSS) was used to assess the severity of stroke on admission. RESULTS: In univariate analysis, the presence of at least one small apo(a) isoform was associated with ischemic stroke in men (p = 0.02) but not in women (p = 0.33). After allowance for age, gender and traditional vascular risk factors, subjects carrying at least one small apo(a) isoform were at increased risk of atherothrombotic stroke (odds ratio [OR] 7.1, 95% CI 2.8 to 17.5, p = 0.00001) but not of lacunar infarction (OR 1.1, 95% CI 0.5 to 2.7, p = 0.78). Multivariate logistic regression analysis revealed that in the atherothrombotic stroke group, the presence of at least one small-sized apo(a) phenotype was associated with an NIHSS score > or =6 (OR 13.6, 95% CI 1.6 to 111.9, p = 0.015). CONCLUSION: Small apolipoprotein (a) isoforms distinguish atherothrombotic stroke from lacunar infarction and are associated with the severity of atherothrombotic stroke.

Apolipoprotein(a) size polymorphism is associated with coronary heart disease in polygenic hypercholesterolemia.

BACKGROUND AND AIM: In addition to high serum cholesterol levels, various cardiovascular risk factors may be involved in the development of coronary heart disease (CHD) in hypercholesterolemic subjects. As the levels of lipoprotein(a) [Lp(a)], an important and independent cardiovascular risk factor, are high in polygenic hypercholesterolemia (PH), we investigated plasma Lp(a) levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of CHD events in PH patients. METHODS AND RESULTS: Lp(a) levels and apo(a) isoforms were determined in 191 PH patients, 83 normocholesterolemic subjects with CHD, and 94 normocholesterolemic controls without CHD. Lp(a) levels were similar in the hypercholesterolemic subjects with (n=100) or without CHD (n=91): 21.4 (range 6.6-59.23) vs 18.5 (range 5.25-57.25) mg/dL (p=NS). Low molecular weight apo(a) isoforms were more prevalent (55%) in the PH patients with CHD, whereas high molecular weight apo(a) isoforms were more prevalent (62.6%) in those without CHD: this difference was significant (p<0.05). A stepwise multiple-discriminant analysis made in order to determine the independence of common cardiovascular risk factors, Lp(a) levels and low molecular weight apo(a) isoforms in predicting CHD among hypercholesterolemic subjects showed that the presence of a positive family history of CHD, smoking, age, and the presence of at least one apo(a) isoform of low molecular weight were independently associated with CHD. CONCLUSIONS: Despite high Lp(a) levels, our findings do not support the hypothesis that Lp(a) plays an independent role in determining clinical CHD in PH subjects. However, the presence of at least one low molecular weight apo(a) isoform is an independent genetic predictor of CHD in hypercholesterolemic subjects. Together with other cardiovascular risk factors, apo(a) phenotypes should be assessed to evaluate the overall CHD risk status of all subjects with high serum cholesterol levels.

[Clinical comparison of different replacement milk formulas in children with allergies to cow's milk proteins. 24-month follow-up study]. / Comparazione clinica di differenti formule di latte sostitutivo in bambini con allergia alle proteine del latte vaccino. Follow-up a 24 mesi.

The elective treatment for allergy to cow's milk protein is the elimination of these proteins from the diet. The present study with a follow-up of over two years took the form of a comparison between different replacement formulas based on soya (group A), hydrolysate of soya and bovine collagen (group B), and hydrolysate of casein (group C), randomly administered to 55 children (30 males and 25 females, aged between 2-48 months) with documented allergy to cow's milk proteins, but with different clinical symptoms. Tests to evaluate the acquisition of clinical tolerance to cow's milk proteins were performed using a day-hospital regime every 6 months. Sensitivity reactions were observed in 22% of cases in group A, 8% in group B and 37.5% in group C. It is worth underlining that 5 of the 6 children with reactions to soya protein then showed an excellent tolerance to hydrolysate of soya when it was administered subsequently until tolerance was achieved. Weight and statutory growth was uniformly good in all three groups. A high percentage of children achieved tolerance after 24 months (72%); the mean time taken to acquire clinical tolerance was 11.6 +/- 4.8 in group A, 11.6 +/- 6.02 in group B, and 14 +/- 5.6 in group C. No correlation was found between the type of initial symptoms, age at onset, method of response to first challenge and the time taken to acquire tolerance.