Management of hypertension during lenvatinib for advanced thyroid cancer: a suggested diagnostic and therapeutic algorithm

Background: Hypertension (HTN) is the most frequent adverse event during treatment with lenvatinib (LEN), but data on its best management are limited. Aim: The objective of this study was to assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care centre cohort. Methods: Twenty-nine patients were followed up for a mean time of 29.8 months (6–77 months). Results: After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with L EN dose and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and proteinuria or clinical features or best morphological response or any other adverse event (AE), with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCBs) due to their effect on vasodilation. In case of poor control, CC Bs were associated with one or more anti-hypertensive drug. Conclusion: HTN is a frequent and early AE in patients on LEN treatment. We suggest a diagnostic and therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation

The G Protein-Coupled Receptor GPR17: Overview and Update

The GPR17 receptor is a G protein-coupled receptor (GPCR) that seems to respond to two unrelated families of endogenous ligands: nucleotide sugars (UDP, UDP-galactose, and UDP-glucose) and cysteinyl leukotrienes (LTD4 , LTC4 , and LTE4 ), with significant affinity at micromolar and nanomolar concentrations, respectively. This receptor has a broad distribution at the level of the central nervous system (CNS) and is found in neurons and in a subset of oligodendrocyte precursor cells (OPCs). Unfortunately, disparate results emerging from different laboratories have resulted in a lack of clarity with regard to the role of GPR17-targeting ligands in OPC differentiation and in myelination. GPR17 is also highly expressed in organs typically undergoing ischemic damage and has various roles in specific phases of adaptations that follow a stroke. Under such conditions, GPR17 plays a crucial role; in fact, its inhibition decreases the progression of ischemic damage. This review summarizes some important features of this receptor that could be a novel therapeutic target for the treatment of demyelinating diseases and for repairing traumatic injury

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

Insight from an Italian Delphi Consensus on EVAR feasibility outside the instruction for use: the SAFE EVAR Study

BACKGROUND: The SAfety and FEasibility of standard EVAR outside the instruction for use (SAFE-EVAR) Study was designed to define the attitude of Italian vascular surgeons towards the use of standard endovascular repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) outside the instruction for use (IFU) through a Delphi consensus endorsed by the Italian Society of Vascular and Endovascular Surgery (Societa Italiana di Chirurgia Vascolare ed Endovascolare - SICVE). METHODS: A questionnaire consisting of 26 statements was developed, validated by an 18 -member Advisory Board, and then sent to 600 Italian vascular surgeons. The Delphi process was structured in three subsequent rounds which took place between April and June 2023. In the first two rounds, respondents could indicate one of the following five degrees of agreement: 1) strongly agree; 2) partially agree; 3) neither agree nor disagree; 4) partially disagree; 5) strongly disagree; while in the third round only three different choices were proposed: 1) agree; 2) neither agree nor disagree; 3) disagree. We considered the consensus reached when &gt;70% of respondents agreed on one of the options. After the conclusion of each round, a report describing the percentage distribution of the answers was sent to all the participants. RESULTS: Two -hundred -forty-four (40.6%) Italian Vascular Surgeons agreed to participate the first round of the Delphi Consensus; the second and the third rounds of the Delphi collected 230 responders (94.3% of the first -round responders). Four statements (15.4%) reached a consensus in the first rounds. Among the 22 remaining statements, one more consensus (3.8%) was achieved in the second round. Finally, seven more statements (26.9%) reached a consensus in the simplified last round. Globally, a consensus was reached for almost half of the proposed statements (46.1%). CONCLUSIONS: The relatively low consensus rate obtained in this Delphi seems to confirm the discrepancy between Guideline recommendations and daily clinical practice. The data collected could represent the source for a possible guidelines' revision and the proposal of specific Good Practice Points in all those aspects with only little evidence available

Comparing Executive Functions in Children and Adolescents with Autism and ADHD—A Systematic Review and Meta-Analysis

Two neurodevelopmental conditions, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), have been associated with executive function (EF) impairments but the specificity of their impairments is still controversial. The present meta-analysis aimed to identify the differences in EF profiles of ASD, ADHD, and ASD+ADHD in relation to a control group of individuals with typical development (TD) and to understand whether the EF performance could change depending upon the type of measure used to assess EF (performance tests vs. questionnaires). Results from 36 eligible studies revealed that ADHD and ASD showed more difficulties than the TD group in tests and, particularly, in questionnaires. No significant differences in the EF profile emerged between ASD and ADHD when assessed through neuropsychological tests (d = 0.02), while significant differences emerged when assessed through questionnaires, with ADHD having higher ratings than ASD (d = −0.34). EF questionnaires and neuropsychological tests may catch two different constructs of EF, with the former being more predictive of everyday life EF impairments. The comparison between the double diagnosis group (ADHD+ASD) and the clinical groups pointed out that the former has a more similar EF profile to the ADHD-alone one and that it shows more difficulties than ASD-alone

Lateral sinus thrombosis as a complication of acute mastoiditis.

Lateral sinus thrombosis is a rare complication of middle ear diseases: in children, it is usually related to acute otitis media, but it is also found in adults with chronic otitis. It was more frequent in the pre-antibiotic era and mortality was high. The Authors present a paediatric case of lateral sinus thrombosis in which they describe the clinical approach and related literature