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Abstract Aims The initial bundle of cares strongly affects haemodynamics and outcomes in acute decompensated heart failure cardiogenic shock (ADHF‐CS). We sought to characterize whether 24 h haemodynamic profiling provides superior prognostic information as compared with admission assessment and which haemodynamic parameters best predict in‐hospital death. Methods and results All patients with ADHF‐CS and with available admission and 24 h invasive haemodynamic assessment from two academic institutions were considered for this study. The primary endpoint was in‐hospital death. Regression analyses were run to identify relevant predictors of study outcome. We included 127 ADHF‐CS patients [65 (inter‐quartile range 52–72) years, 25.2% female]. Overall, in‐hospital mortality occurred in 26.8%. Non‐survivors were older, with greater CS severity. Among admission variables, age [odds ratio (OR) = 1.06; 95% confidence interval (CI): 1.02–1.11; Padj = 0.005] and CPIRAP (OR = 0.62 for 0.1 increment; 95% CI: 0.39–0.95; Padj = 0.034) were found significantly associated with in‐hospital death. Among 24 h haemodynamic univariate predictors of in‐hospital death, pulmonary elastance (PaE) was the strongest (area under the curve of 0.77; 95% CI: 0.68–0.86). PaE (OR = 5.98; 95% CI: 2.29–17.48; Padj

Abstract Background Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. Methods Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35–70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). Results After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. Conclusions Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

BackgroundPhysical activity is well known to have beneficial effects on glycemic control and to reduce risk factors for cardiovascular disease in persons with type 2 diabetes. Yet, successful implementation of lifestyle interventions targeting physical activity in primary care has shown to be difficult. Smartphone apps may provide useful tools to support physical activity. The DiaCert app was specifically designed for integration into primary care and is an automated mobile health (mHealth) solution promoting daily walking. ObjectiveThis study aimed to investigate the effect of a 3-month-long intervention promoting physical activity through the use of the DiaCert app among persons with type 2 diabetes in Sweden. Our primary objective was to assess the effect on moderate to vigorous physical activity (MVPA) at 3 months of follow-up. Our secondary objective was to assess the effect on MVPA at 6 months of follow-up and on BMI, waist circumference, hemoglobin A1c, blood lipids, and blood pressure at 3 and 6 months of follow-up. MethodsWe recruited men and women with type 2 diabetes from 5 primary health care centers and 1 specialized center. Participants were randomized 1:1 to the intervention or control group. The intervention group was administered standard care and access to the DiaCert app at baseline and 3 months onward. The control group received standard care only. Outcomes of objectively measured physical activity using accelerometers, BMI, waist circumference, biomarkers, and blood pressure were assessed at baseline and follow-ups. Linear mixed models were used to assess differences in outcomes between the groups. ResultsA total of 181 study participants, 65.7% (119/181) men and 34.3% (62/181) women, were recruited into the study and randomized to the intervention (n=93) or control group (n=88). The participants’ mean age and BMI were 60.0 (SD 11.4) years and 30.4 (SD 5.3) kg/m2, respectively. We found no significant effect of the intervention (group by time interaction) on MVPA at either the 3-month (β=1.51, 95% CI –5.53 to 8.55) or the 6-month (β=–3.53, 95% CI –10.97 to 3.92) follow-up. We found no effect on any of the secondary outcomes at follow-ups, except for a significant effect on BMI at 6 months (β=0.52, 95% CI 0.20 to 0.84). However, mean BMI did not differ between the groups at the 6-month follow-up. ConclusionsWe found no evidence that persons with type 2 diabetes being randomized to use an app promoting daily walking increased their levels of MVPA at 3 or 6 months’ follow-up compared with controls receiving standard care. The effect of the app on BMI was unclear, and we found nothing to support an effect on secondary outcomes. Further research is needed to determine what type of mHealth intervention could be effective to increase physical activity among persons with type 2 diabetes. Trial RegistrationClinicalTrials.gov NCT03053336; https://clinicaltrials.gov/study/NCT03053336

Abstract We continue our study of multipoint correlators of scalar fields on the 1d defect CFT generated by inserting operators along the Maldacena-Wilson line in N $$ \mathcal{N} $$ = 4 SYM. We present a weak-coupling recursion relation that captures correlators at next-to-leading order involving an arbitrary number of the elementary scalar fields ϕ i and ϕ 6, the latter being unprotected. We can then build correlators of composite operators by pinching the scalar fields together. As a demonstration of our method, we give explicit results for correlators containing up to six points. We also expand some selected correlators using recently obtained conformal blocks in the comb and snowflake channel, and check that the extracted low-lying CFT data is consistent with explicit computations.

We reported a case of blood culture–negative infective endocarditis on a native valve, where the clinical presentation was exclusively related to extensive cerebral ischemia secondary to multiple systemic septic cardioembolic events. The cause was ascribed to subacute Bartonella henselae infection, presumably transmitted by cat scratch, documented by positive serologic findings.

Non-specific lipid transfer proteins (nsLTPs) are a family of plant pan-allergens that represent the primary cause of food allergies in the Mediterranean area, characterized by a wide range of clinical manifestations, ranging from the total absence of symptoms up to anaphylaxis. This wide variety of symptoms is related to the intrinsic capacity of nsLTPs to cause an allergic reaction in a specific subject, but also to the presence of co-factors exacerbating (i.e., exercise, NSAIDs, PPIs, alcohol, cannabis, prolonged fasting, menstruation, acute infections, sleep deprivation, chronic urticaria) or protecting from (i.e., co-sensitization to PR10, profilin or polcalcin) severe reactions. In this picture, recognizing some nsLTPs-related peculiarities (i.e., route, type and number of sensitizations, concentration of the allergen, cross-reactions) and eventual co-factors may help the allergist to define the risk profile of the single patient, in order to promote the appropriate management of the allergy from dietary advices up to the prescription of life-saving epinephrine autoinjector.

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Abstract We study multipoint correlators of protected scalars on the Maldacena-Wilson line in N $$ \mathcal{N} $$ = 4 SYM. Working at weak coupling in the planar limit, we derive an explicit recursion relation that captures next-to-leading order correlators with an arbitrary number of insertions of the fundamental scalar field. By pinching fundamental scalars together, we can build composite protected operators with higher values of the R-charge. Our result then encompasses arbitrary n-point correlators of protected operators with arbitrary weight. As a demonstration of our method, we give explicit formulae for correlators with up to six points. Using these results we observe that all our correlators are annihilated by a special class of differential operators. We conjecture that these differential operators are non-perturbative constraints and can be considered a multipoint extension of the superconformal Ward identities satisfied by four-point functions.

Abstract Aim We investigated the prognostic significance of serum potassium abnormalities at discharge in patients hospitalized for acute heart failure (AHF). Methods and results In a retrospective analysis, we included 926 patients hospitalized for AHF, stratified by serum potassium levels at discharge as hypokalaemia (5.0 mEq/L). The primary endpoint was all‐cause death at 1 year since hospital discharge. At discharge, 40 patients had hypokalaemia (4.3%), 840 normokalaemia (90.7%), and 46 hyperkalaemia (5.0%). Patients with hyperkalaemia at discharge were more frequently men, had more signs of congestion, and lower LVEF while patients with hypokalaemia were more likely to be women with HFpEF. Treatment with ACEi/ARBs and MRAs ≥50% of target dose at discharge was similar across groups. One year all‐cause death occurred in 10% of the patients with hypokalaemia, 13.9% of those with normokalaemia, and 30.4% of those with hyperkalaemia (P = 0.006). After adjustment for covariates, including renal function, background treatment, and baseline potassium level, hyperkalaemia resulted an independent predictor of the primary endpoint (HR 1.96, 95% IC [1.01–3.82]; P = 0.048). Conclusions In patients with AHF, the presence of hyperkalaemia at discharge is an independent predictor of 1 year all‐cause death.

On May 2020, after 2 months of online teaching with no face-to-face lectures, the Education Committee of the Italian scientific Society of Medical Statistics and Clinical Epidemiology conceived an online survey to assess satisfaction of Italian academics of medical statistics with online teaching and remote exams. This survey highlighted teachers' perceptions as well as opportunities and limitations of online teaching of medical statistics, biostatistics, and epidemiology. Although 61% of Italian academics of medical statistics declared to be favorable to provide online teaching of medical statistics, biostatistics, and epidemiology in the future, we recognize that distance education cannot substitute the unique value of teaching and knowledge exchange that could only be transmitted through a personal interaction between students and teachers. These indications may be useful to improve the quality of the teaching process in the future.

Fish roe are not yet described as triggers of allergic reactions in Italy, especially during the pediatric age; they are more frequently involved in anaphylaxis in Eastern countries, such as Japan. For this report, we reported a case of anaphylaxis in a 2-year-old boy admitted to our Hospital Pediatric Emergency Room with a suspected allergic reaction. 15 min after the meal, he presented generalized urticaria, angioedema, wheezing, sneezing, and two vomiting episodes. The meal was smoked salmon, butter, mayonnaise, anchovies, and fish roe (salmon and lumpfish roe). Tryptase serum levels presented as elevated in the acute phase and normal after 24 h. Serum food-specific IgE tested negative for salmon and other fish, such as skin prick tests. Serum food-specific IgE showed that the patient was sensitized to cow’s milk and eggs, but he doesn’t have a food allergy. He had regularly consumed milk and eggs before and after the allergic reaction without clinical problems. A prick-by-prick test resulted positive for fish roe (salmon and lumpfish roe). Based on patient’s history, allergy test results in vivo, and tryptase serum levels, the diagnosis of anaphylaxis induced by fish roe was confirmed. In conclusion, to the best of our knowledge, this is the first pediatric case of fish roe-induced anaphylaxis reported in Italy.

Aims: The initial bundle of cares strongly affects haemodynamics and outcomes in acute decompensated heart failure cardiogenic shock (ADHF‐CS). We sought to characterize whether 24 h haemodynamic profiling provides superior prognostic information as compared with admission assessment and which haemodynamic parameters best predict in‐hospital death. Methods and results: All patients with ADHF‐CS and with available admission and 24 h invasive haemodynamic assessment from two academic institutions were considered for this study. The primary endpoint was in‐hospital death. Regression analyses were run to identify relevant predictors of study outcome. We included 127 ADHF‐CS patients [65 (inter‐quartile range 52–72) years, 25.2% female]. Overall, in‐hospital mortality occurred in 26.8%. Non‐survivors were older, with greater CS severity. Among admission variables, age [odds ratio (OR) = 1.06; 95% confidence interval (CI): 1.02–1.11; Padj = 0.005] and CPIRAP (OR = 0.62 for 0.1 increment; 95% CI: 0.39–0.95; Padj = 0.034) were found significantly associated with in‐hospital death. Among 24 h haemodynamic univariate predictors of in‐hospital death, pulmonary elastance (PaE) was the strongest (area under the curve of 0.77; 95% CI: 0.68–0.86). PaE (OR = 5.98; 95% CI: 2.29–17.48; Padj < 0.001), pulmonary artery pulsatility index (PAPi, OR = 0.77; 95% CI: 0.62–0.92; Padj = 0.013) and age (OR = 1.06; 95% CI: 1.02–1.11; Padj = 0.010) were independently associated with in‐hospital death. Best cut‐off for PaE was 0.85 mmHg/mL and for PAPi was 2.95; cohort phenotyping based on these PaE and PAPi thresholds further increased in‐hospital death risk stratification; patients with 24 h high PaE and low PAPi exhibited the highest in‐hospital mortality (56.2%). Conclusions: Pulmonary artery elastance has been found to be the most powerful 24 h haemodynamic predictor of in‐hospital death in patients with ADHF‐CS. Age, 24 h PaE, and PAPi are independently associated with hospital mortality. PaE captures ventricular (RV) afterload mismatch and PAPi provides a metric of RV adaptation, thus their combination generates four distinct haemodynamic phenotypes, enhancing in‐hospital death risk stratification. [ABSTRACT FROM AUTHOR]

Abstract Aims Myocardial injury (MI) in coronavirus disease‐19 (COVID‐19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in‐hospital evolution of MI and its prognostic impact. Methods and results We performed an analysis from an Italian multicentre study enrolling COVID‐19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in‐hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P

Abstract We define a Mellin amplitude for CFT1 four-point functions. Its analytical properties are inferred from physical requirements on the correlator. We discuss the analytic continuation that is necessary for a fully nonperturbative definition of the Mellin transform. The resulting bounded, meromorphic function of a single complex variable is used to derive an infinite set of nonperturbative sum rules for CFT data of exchanged operators, which we test on known examples. We then consider the perturbative setup produced by quartic interactions with an arbitrary number of derivatives in a bulk AdS2 field theory. With our formalism, we obtain a closed-form expression for the Mellin transform of tree-level contact interactions and for the first correction to the scaling dimension of “two-particle” operators exchanged in the generalized free field theory correlator.

Introduction: Lipid transfer proteins (nsLTPs) are ubiquitous allergens. Patients affected by nsLTP syndrome experience symptoms to various plant-derived foods, ranging from local manifestations to anaphylaxis, the critical treatment of which is represented by self-administration of adrenaline. The principle aim of this study is to assess how dietary recommendations influence the occurrence of new and severe cases and if poly-sensitization to different nsLTPs may play a role. We also investigated about the appropriate use of adrenaline auto-injector during the episodes of anaphylaxis. Moreover, we examinated how other features (ie, co-sensitization to profilin and PR-10 and the presence of risk co-factors) affect these events. Materials and methods: We evaluated 78 patients allergic to nsLTPs, investigating adherence to diet and ability to use the adrenaline auto-injector. Number of sensitization to nsLTPs, co-sensitization to other panallergens, and presence of risk factors for new reactions were also assessed. Diagnosis was based on clinical history and positivity to in vivo and in vitro tests. During the follow-up, compliance, diet modifications, and new reactions were noted, and re-training for the use of epinephrine auto-injector was performed. At the last visit we evaluated the patients’ ability to use the self-injector. Results: The whole of fruits belonging to the Rosaceae family emerged as the most frequent culprit foods (28%), followed by walnut (17%), peanut (17%), and hazelnut (10%). At the baseline visit 23% of the patients described the presence of a risk factor during the allergic reaction (mainly nonsteroidal anti-inflammatory drugs [NSAIDs] and exercise). Forty-five percent of the patients reported anaphylactic reactions; no association between the type of food and the severity of the reactions was found. The presence of sensitization to 4 or more nsLTPs was associated to more severe reactions (p < .05; OR 1.67). During the follow-up 38% of the patients experienced at least 1 new allergic reaction: in 79% of them the culprit food was previously tolerated, and in 69% the reaction was an anaphylaxis. Only 47% of the patients showed a proper use of adrenaline auto-injector during the final evaluation, but a significant correlation between periodic education and reduction of the probability of mistakes in the use was reported (p < .05; OR 0.34). Furthermore, an association between co-sensitization to PR-10 (in particular Bet v1) and profilin and less severe symptoms was found, but without a significant odds ratio. Conclusion: A careful education aimed to the prevention of new reactions, through dietary restrictions and avoidance of risk co-factors, and to the management of anaphylaxis, through the training for the correct use of adrenaline auto-injector, should be a routine practice in nsLTP syndrome.

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly. Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods. Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro. Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p

Abstract Aims Treatment with angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptors blockers (ARBs) and beta‐blockers is frequently suboptimal at discharge in patients hospitalized for acute heart failure (AHF). We investigated the prognostic significance of medical treatment at discharge and its changes during hospitalization. Methods and results In a retrospective analysis, we included 623 patients hospitalized for AHF with reduced left ventricular ejection fraction (