Trustworthy management in hospital settings: a systematic review.

BACKGROUND: Trustful relationships play a vital role in successful organisations and well-functioning hospitals. While the trust relationship between patients and providers has been widely studied, trust relations between healthcare professionals and their supervisors have not been emphasised. A systematic literature review was conducted to map and provide an overview of the characteristics of trustworthy management in a hospital setting. METHODS: We searched Web of Science, Embase, MEDLINE, APA PsycInfo, CINAHL, Scopus, EconLit, Taylor & Francis Online, SAGE Journals and Springer Link from database inception up until Aug 9, 2021. Empirical studies written in English undertaken in a hospital or similar setting and addressed trust relationships between healthcare professionals and their supervisors were included, without date restrictions. Records were independently screened for eligibility by two researchers. One researcher extracted the data and another one checked the correctness. A narrative approach, which involves textual and tabular summaries of findings, was undertaken in synthesising and analysing the data. Risk of bias was assessed independently by two researchers using two critical appraisal tools. Most of the included studies were assessed as acceptable, with some associated risk of bias. RESULTS: Of 7414 records identified, 18 were included. 12 were quantitative papers and 6 were qualitative. The findings were conceptualised in two categories that were associated with trust in management, namely leadership behaviours and organisational factors. Most studies (n = 15) explored the former, while the rest (n = 3) additionally explored the latter. Leadership behaviours most commonly associated with employee's trust in their supervisors include (a) different facets of ethical leadership, such as integrity, moral leadership and fairness; (b) caring for employee's well-being conceptualised as benevolence, supportiveness and showing concern and (c) the manager's availability measured as being accessible and approachable. Additionally, four studies found that leaders' competence were related to perceptions of trust. Empowering work environments were most commonly associated with trust in management. CONCLUSIONS: Ethical leadership, caring for employees' well-being, manager's availability, competence and an empowering work environment are characteristics associated with trustworthy management. Future research could explore the interplay between leadership behaviours and organisational factors in eliciting trust in management.

Assessing the Effects of Medical Information on Parental Self-Medication Behaviors for Children's Health: A Comparative Analysis.

Background and Objectives: Health professionals have voiced concerns about the danger of self-medication in times of growing use of over-the-counter medicines and, in some contexts, the unregulated selling of them. Previous research has examined the incidence of parental self-medication as well as the use and abuse of antibiotics without medical advice. However, these studies have limited evidence on the role of family doctors and the perceived severity of self-medication in the case of parents. Based on the Health Belief Model, our research tested the effects of exposure to medical information on the parents' attitudes toward self-treating their children, without medical advice. Specifically, we aimed to assess whether exposure to information warning about the risks of treating children without a medical prescription influences parents' attitudes toward administering medicines to their children without medical advice. Materials and Methods: 210 parents engaged in the study, and were divided into two groups. One group was exposed to educational materials related to the perils of self-medication and the second one was not. All participants answered the same questionnaire and the answers were compared between the two groups. Results: The results showed that our respondents evaluated the practices of self-medication negatively (a higher score indicates a more negative evaluation), especially when it came to treating their children without medical advice (3.91 ± 1.04 for unexposed and 3.98 ± 1.08 for exposed). However, their attitudes towards self-medication varied depending on their beliefs about administering certain medications. Both those exposed to the warning information and those who were not exposed have agreed that they are unable to avoid treatment of their ill child without medical advice. Conclusions: In general, our respondents evaluate negatively the practices of self-medication, especially the treatment of their children without medical advice. Therefore, future health education campaigns need to be targeted specifically, with messages that guide how to act in particular cases depending on the medication used and the child's condition.

Patterns of progression in patients treated for immuno-oncology antibodies combination.

BACKGROUND: New patterns of progression under immune-oncology (IO) antibodies (mAb) have been described such as pseudoprogression. Except for melanoma, variations between studies reveal difficulties to establish their prevalence. METHODS: This retrospective study enrolled patients participating in IO phase I trials at Gustave Roussy cancer center for solid tumors excluding melanoma. Radiological assessment according to iRECIST was correlated with prospectively registered patient characteristics and outcomes. Pseudoprogression (PsPD) was defined as RECIST-defined progression followed by stabilization or decrease at the next imaging, and dissociated response (DisR) as concomitant decrease in some tumor lesions and increase in others at a same timepoint. RESULTS: Among 360 patients included, 74% received IO mAb combination: 45% with another IO mAb, 20% with targeted therapy and 10% with radiotherapy. The overall response rate was 19.7%. PsPD were observed in 10 (2.8%) patients and DisR in 12 (3.3%) patients. Atypical responses (AR), including PsPD and DisR, were not associated with any patient's baseline characteristics. Compare with typical responder patients, patients experiencing AR presented a shorter iPFS (HR 0.34; p < 0.001) and OS (HR 0.27; p = 0.026). Among the 203 patients who progressed in 12 weeks, 80 (39.4%) patients were treated beyond progression. PD was confirmed in 80% of cases, while 10% of patients presented a response. CONCLUSION: Pseudoprogression and dissociated response are uncommon patterns of progression. Their prevalence should be balanced with the rate of real progressing patients treated beyond progression. Prognosis or on-treatment biomarkers are needed to identify early patients who will benefit from immunotherapy.

A 2021 Update on the Use of Liraglutide in the Modern Treatment of 'Diabesity': A Narrative Review.

Obesity and type 2 diabetes mellitus have become a significant public health problem in the past decades. Their prevalence is increasing worldwide each year, greatly impacting the economic and personal aspects, mainly because they frequently coexist, where the term "diabesity" may be used. The drug class of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is one of the most modern therapy options in managing these metabolic disorders. This review focuses on the effects of liraglutide, a long-acting GLP-1 RA, in diabesity and non-diabetic excess weight. This drug class improves glycemic control by enhancing insulin secretion from the beta-pancreatic cells and inhibiting glucagon release. Furthermore, other effects include slowing gastric emptying, increasing postprandial satiety, and reducing the appetite and food consumption by influencing the central nervous system, with weight reduction effects. It also reduces cardiovascular events and has positive effects on blood pressure and lipid profile. A lower-dose liraglutide (1.2 or 1.8 mg/day) is used in patients with diabetes, while the higher dose (3.0 mg/day) is approved as an anti-obesity drug. In this review, we have summarized the role of liraglutide in clinical practice, highlighting its safety and efficacy as a glucose-lowering agent and a weight-reduction drug in patients with and without diabetes.

Pregnancy experiences of women in rural Romania: understanding ethnic and socioeconomic disparities.

Women in rural Romania face significant health disadvantages. This qualitative pilot study describes the structural disadvantage experienced during pregnancy by women in rural Romania, focusing on the lived experiences of Roma women. We explore how women in rural communities experience pregnancy, their interactions with the healthcare system, and the role that ethnic and social factors play in pregnancy and childbearing. We conducted 42 semi-structured interviews with health and other professionals, seven narrative interviews with Roma and non-Roma women and a focus group with Roma women. Data were analysed using thematic analysis. We identified intersectional factors associated with women's pregnancy experiences: women perceiving pregnancy as both unplanned and wanted, joyful, and normal; women's and professionals' differing prenatal care perceptions; transport and cost related barriers to care; socioeconomic and ethnic discrimination; and facilitators to care such as social support, having a health mediator and having a doctor. Talking directly with professionals and Roma and non-Roma women helped us understand these many factors, how they are interconnected, and how we can work towards improving the pregnancy experiences of Roma women in rural Romania.

Phase I trial of bortezomib daily dose: safety, pharmacokinetic profile, biological effects and early clinical evaluation in patients with advanced solid tumors.

Purpose This phase I study investigated bortezomib in solid tumors used as a daily subcutaneous regimen. Previous regimens showed only modest activity in solid tumors which was potentially related to sub-optimal tumor penetration. We aimed at exploring if daily low dose administration of bortezomib may allow a greater and tolerable pharmacokinetic exposure which might be required for antitumor activity in solid tumors. Patients and methods This 3 + 3 design, dose escalation, monocentric study aimed at defining the maximum tolerated dose of daily low dose schedule of bortezomib. Tolerability, pharmacokinetics, pharmacodynamics, antitumor activity, biomarkers for proteasome inhibition, pre- and post-treatment tumor biopsies were also evaluated. Results A total of eighteen patients were dosed in 3 bortezomib cohorts (0.5, 0.6 and 0.7 mg/m2), with 3, 11 and 4 patients respectively. Three patients experienced dose-limiting toxicities: Grade (G) 3 Sweet's syndrome (at 0.6 mg/m2), G3 asthenia and anorexia or ataxia (2 patients at 0.7 mg/m2). The most common study drug-related adverse events (all grades) were thrombocytopenia (72%), fatigue (56%), neuropathy (50%), anorexia (44%) and rash (39%). Dose 0.6 mg/m2 of bortezomib was considered as the recommended phase II dose. A significant tumor shrinkage (-36% according to WHO criteria) was observed in one patient with heavily pre-treated GIST, and 2 minor responses (-20%) were recorded in two patients with melanoma and mesothelioma. Conclusion This daily subcutaneous regimen of bortezomib showed a dose dependent plasma exposure, evidence of target inhibition and preliminary signs of clinical activity. However, cumulative neurological toxicity of this dose-dense daily regimen might preclude its further clinical development.

A Sensitive Public Health Issue-The Vaccine Acceptancy and the Anti-Pertussis Immune Status of Pregnant Women from a Romanian Metropolitan Area.

(1) Background: Immunization of pregnant women (PWs) against Bordetella pertussis infection is still a challenging health matter. (2) Methods: We gathered questionnaire data from 180 PWs regarding their expectancies and current opinion on infectious disease prevention. For the group of PWs who agreed to further investigations, the serum levels of Ig G anti-B. pertussis antibodies (IgG-PT) titer were measured and analyzed. (3) Results: A total of 180 PWs completed the questionnaire and 98 (54.44%, study group) accepted to perform the laboratory tests. During the first two pregnancy trimesters, PWs were found to be more willing (compared with the control group) to test for identifying high-risk situations that could affect themselves and their future infant (p < 0.001). Most of the participating PWs (91, 91.9%) had low levels of anti-pertussis antibodies (values < 40 IU/mL). Declared vaccine coverage of the PWs newborn infants for DTaP-1 and Prevenar 13 (at 2 months) and DTaP-2 and Prevenar 13 (at 4 months) vaccination reached 100% in the study group, while in the control group only 30/82 (36.59%) PWs accepted to be vaccinated during pregnancy, none of them providing data on their infants' vaccine coverage. (4) Conclusions: Enrolled PWs faced a waning immunity against the B. pertussis infection. By raising maternal confidence in the protective role of vaccines against infectious diseases, better vaccine acceptance and better infant vaccine coverage can be achieved.

FIP1L1-PDGFRα-Positive Loeffler Endocarditis-A Distinct Cause of Heart Failure in a Young Male: The Role of Multimodal Diagnostic Tools.

The presence of the Fip1-Like1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) fusion gene represents a rare cause of hypereosinophilic syndrome (HES), which is associated with organ damage. The aim of this paper is to emphasize the pivotal role of multimodal diagnostic tools in the accurate diagnosis and management of heart failure (HF) associated with HES. We present the case of a young male patient who was admitted with clinical features of congestive HF and laboratory findings of hypereosinophilia (HE). After hematological evaluation, genetic tests, and ruling out reactive causes of HE, a diagnosis of positive FIP1L1-PDGFRα myeloid leukemia was established. Multimodal cardiac imaging identified biventricular thrombi and cardiac impairment, thereby raising suspicion of Loeffler endocarditis (LE) as the cause of HF; this was later confirmed by a pathological examination. Despite hematological improvement under corticosteroid and imatinib therapy, anticoagulant, and patient-oriented HF treatment, there was further clinical progression and subsequent multiple complications (including embolization), which led to patient death. HF is a severe complication that diminishes the demonstrated effectiveness of imatinib in the advanced phases of Loeffler endocarditis. Therefore, the need for an accurate identification of heart failure etiology in the absence of endomyocardial biopsy is particularly important for ensuring effective treatment.

The Gender Gap in Aortic Dissection: A Prospective Analysis of Risk and Outcomes.

Aortic dissection (AD) is a severe cardiovascular condition that could have negative consequences. Our study employed a prospective design and examined preoperative, perioperative, and postoperative data to evaluate the effects of gender on various medical conditions. We looked at how gender affected the results of aortic dissection (AD). In contrast to female patients who had more systemic hypertension (p=0.031), male patients had higher rates of hemopericardium (p=0.003), pulmonary hypertension (p=0.039), and hemopericardium (p=0.003). Dobutamine administration during surgery significantly raised the mortality risk (p=0.015). There were noticeably more women patients (p=0.01) in the 71 to 80 age group. Significant differences in age (p=0.004), eGFR at admission (p=0.009), and eGFR at discharge (p=0.006) were seen, however, there was no association between gender and mortality. In conclusion, our findings highlight that gender may no longer be such an important aspect of aortic dissection disease as we previously thought, and this information could have an important contribution for surgeons as well as for anesthesiologists involved in the management of acute aortic dissection.

The Pathophysiology and Management of Diabetic Ketoacidosis in COVID-19 Patients: a Literature Review.

Diabetic individuals are considered a vulnerable population during the COVID-19 Pandemic, and several studies noted worse outcomes, including death, among those who get infected. Diabetic emergencies, such as ketoacidosis (DKA), are common and potentially life-threatening conditions in uncontrolled patients. While the pathophysiological background of the relationship between COVID-19 and DKA is not fully understood, early reports available so far indicate that patients with pre-existing diabetes who get infected with the SARS-CoV 2 virus are at higher risk of DKA. It was also suggested that DKA is a poor prognostic sign for infected patients, these being at higher risk of developing worse forms of COVID-19 disease and having high mortality. Therefore, healthcare personnel dealing with such patients face a considerable challenge, as the correct and safe emergency management of such cases is far from established. This article aimed to conduct a study that reviews the current published data available about patients with DKA and COVID-19.

Predicting Immunotherapy Outcomes in Older Patients with Solid Tumors Using the LIPI Score.

Immunotherapy with immune checkpoint blockers (ICB) represents a valid therapeutic option in older patients for several solid cancer types. However, most of the data concerning efficacy and adverse events of ICB available are derived from younger and fitter patients. Reliable biomarkers are needed to better select the population that will benefit from ICB especially in older patients who may be at a higher risk of developing immune-related adverse events (irAEs) with a greater impact on their quality of life. The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/[leukocytes − neutrophils]) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients treated with ICB in non-small-cell lung cancer. We aimed to assess the impact of LIPI in ICB outcomes in a dedicated cohort of older patients. The primary objective was to study the prognostic role of LIPI score in patients aged 70 years or above in a real-life population treated with anti-programmed death-(ligand)1 (anti PD-(L)1). dNLR and LDH were collected in a prospective cohort of patients aged 70 years or above treated with PD-(L)1 inhibitors with metastatic disease between June 2014 and October 2017 at Gustave Roussy. LIPI categorizes the population into three different prognostic groups: good (dNLR ≤ 3 and LDH ≤ ULN­upper normal limit), intermediate (dNLR > 3 or LDH > ULN), and poor (dNLR > 3 and LDH > ULN). Anti PD-(L)1 benefit was analyzed according to overall survival (OS), progression free survival (PFS), and overall response rate (ORR) using RECIST v1.1. criteria. In the 191 older patients treated, most of them (95%) were ICB-naïve, and 160 (84%) had an ECOG performance status of 0−1 with a median age at ICB treatment of 77 (range, 70−93). The most common tumor types were melanoma (66%) and non-small-cell lung cancer (15%). The median follow-up duration was 18.8 months (95% CI 14.7−24.2). LIPI classified the population into three different groups: 38 (23%) patients had a good LIPI score, 84 (51%) had an intermediate LIPI score, and 43 (26%) had a poor LIPI score. The median OS was 20.7 months [95% CI, 12.6−not reached] compared to 11.2 months [95% CI, 8.41−22.2] and 4.7 months [95% CI, 2.2−11.3] in patients with a good, intermediate, and poor LIPI score, respectively (p = 0.0003). The median PFS was 9.2 months [95% CI, 6.2−18.1] in the good LIPI group, 7.2 months [95% CI, 5.4−13] in the intermediate LIPI group, and 3.9 months [95% CI, 2.3−8.2] in the poor LIPI group (p = 0.09). The rate of early death (OS < 3 months) was 37% in the poor LIPI group compared to 5% in the good LIPI group (<0.001). Poor LIPI score was associated with a poorer outcome in older patients treated with anti PD-(L)1. LIPI is a simple and accessible worldwide tool that can serve as a prognostic factor and can be useful for stratification benefit from ICB.

Genome-driven medicine for patients with recurrent glioma enrolled in early phase trials.

BACKGROUND: Recent studies showed that patients with glioma can safely participate in early phase clinical trials; however, clinical benefits in this population were limited. We aimed to evaluate the benefit of molecular profiling to guide enrolment in early phase trials for patients with recurrent glioma. METHODS: Records of patients enrolled in early phase trials of cytotoxic therapies, small molecule inhibitors or monoclonal antibodies from 2008 to 2018 were reviewed for clinico-pathological characteristics, toxicity, response, progression-free survival and overall survival (OS). The primary objective was to evaluate response rates in molecularly-oriented versus non-molecularly-oriented patients. RESULTS: Eighty-eight patients were enrolled, of whom 45 (51.1%) patients were molecularly-oriented. Targets included IDH1/2 (n = 15), BRAF (n = 11), and FGFR1 (n = 3) mutations, FGFR2-3 fusions (n = 9), and mismatch repair deficiency (n = 7). Among patients with high-grade glioma (n = 74), the rate of stable disease ≥6 months and partial or complete response was 25.7% in molecularly-oriented versus 5.1% in non-molecularly-oriented patients (p = 0.02). Upon multivariable adjustment, baseline steroid use ≥20 mg prednisone equivalent per day was associated with shorter OS (OR 3.15 [95% CI 1.62-6.13], p = 0.0008), while molecular enrichment strategy was associated with longer OS (OR 0.40 [95% CI 0.22-0.73], p = 0.003). Nine (10.2%) patients experienced grade 3-4 toxicity and no dose limiting toxicity (DLT) occurred in both cohorts. CONCLUSION: The use of molecular profiling to guide enrolment in early phase trials is feasible and might provide benefits to selected patients with glioma. Further studies are warranted to confirm these results in larger randomised settings and identify the patients most likely to benefit from this approach.

Safety, recommended dose, efficacy and immune correlates for nintedanib in combination with pembrolizumab in patients with advanced cancers.

BACKGROUND: We aimed to determine the safety and efficacy of nintedanib, an oral anti-angiogenic tyrosine kinase inhibitor, in combination with pembrolizumab, an anti-PD1 immunotherapy, in patients with advanced solid tumors (PEMBIB trial; NCT02856425). METHODS: In this monocentric phase Ib dose escalation cohort, we evaluated escalating doses of nintedanib (Dose level 1 (DL1) = 150 mg bid [bis in die, as twice a day]; DL2 = 200 mg bid, oral delivery) in combination with pembrolizumab (200 mg Q3W, IV). Patients received a 1-week lead-in dose of nintedanib monotherapy prior starting pembrolizumab. The primary objective was to establish the maximum tolerated dose (MTD) of the combination based on dose limiting toxicity (DLT) occurrence during the first 4 weeks. Secondary objectives were to assess the anti-tumor efficacy and to identify the associated immune and angiogenic parameters in order to establish the recommended nintedanib dose for expansion cohorts. Flow cytometry (FC), Immuno-Histo-Chemistry (IHC) and electrochemiluminescence multi-arrays were prospectively performed on baseline & on-treatment tumor and blood samples to identify immune correlates of efficacy. RESULTS: A total of 12/13 patients enrolled were evaluable for DLT (1 patient withdrew consent prior receiving pembrolizumab). Three patients at 200 mg bid experienced a DLT (grade 3 liver enzymes increase). Four patients developed grade 1-2 immune related adverse events (irAE). Eight patients died because of cancer progression. Median follow-up was 23.7 months (95%CI: 5.55-40.5). Three patients developed a partial response (PR) (ORR = 25%) and five patients (42%) had durable clinical benefit (DCB), defined as PR or stable disease (SD) ≥ 6 months. At baseline, patients with DCB had higher plasma levels of Tie2, CXCL10, CCL22 and circulating CD4+ PD1+ OX40+ T cells than patients without DCB. Patients with DCB presented also with more DC-LAMP+ dendritic cells, CD3+ T cells and FOXP3+ Tregs in baseline tumor biopsies. For DCB patients, the nintedanib lead-in monotherapy resulted in higher blood CCL3, Tregs and CCR4+ CXCR3+ CXCR5- memory CD4 T cells. After the first pembrolizumab infusion, patients with DCB showed lower IL-6, IL-8, IL-27 plasma levels. CONCLUSION: Nintedanib 150 mg bid is the recommended dose for combination with pembrolizumab and is currently investigated in multiple expansion cohorts. Early tumoral and circulating immune factors were associated with cancer outcome under nintedanib & pembrolizumab therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02856425 . Registered August 4, 2016 - Prospectively registered.

Past, Present, and Future of Blood Biomarkers for the Diagnosis of Acute Myocardial Infarction-Promises and Challenges.

Despite important advancements in acute myocardial infarction (AMI) management, it continues to represent a leading cause of mortality worldwide. Fast and reliable AMI diagnosis can significantly reduce mortality in this high-risk population. Diagnosis of AMI has relied on biomarker evaluation for more than 50 years. The upturn of high-sensitivity cardiac troponin testing provided extremely sensitive means to detect cardiac myocyte necrosis, but this increased sensitivity came at the cost of a decrease in diagnostic specificity. In addition, although cardiac troponins increase relatively early after the onset of AMI, they still leave a time gap between the onset of myocardial ischemia and our ability to detect it, thus precluding very early management of AMI. Newer biomarkers detected in processes such as inflammation, neurohormonal activation, or myocardial stress occur much earlier than myocyte necrosis and the diagnostic rise of cardiac troponins, allowing us to expand biomarker research in these areas. Increased understanding of the complex AMI pathophysiology has spurred the search of new biomarkers that could overcome these shortcomings, whereas multi-omic and multi-biomarker approaches promise to be game changers in AMI biomarker assessment. In this review, we discuss the evolution, current application, and emerging blood biomarkers for the diagnosis of AMI; we address their advantages and promises to improve patient care, as well as their challenges, limitations, and technical and diagnostic pitfalls. Questions that remain to be answered and hotspots for future research are also emphasized.

The SGLT-2 Inhibitors in Personalized Therapy of Diabetes Mellitus Patients.

Diabetes mellitus (DM) represents a major public health problem, with yearly increasing prevalence. DM is considered a progressive vascular disease that develops macro and microvascular complications, with a great impact on the quality of life of diabetic patients. Over time, DM has become one of the most studied diseases; indeed, finding new pharmacological ways to control it is the main purpose of the research involved in this issue. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are a modern drug class of glucose-lowering agents, whose use in DM patients has increased in the past few years. Besides the positive outcomes regarding glycemic control and cardiovascular protection in DM patients, SGLT-2i have also been associated with metabolic benefits, blood pressure reduction, and improved kidney function. The recent perception and understanding of SGLT-2i pathophysiological pathways place this class of drugs towards a particularized patient-centered approach, moving away from the well-known glycemic control strategy. SGLT-2i have been shown not only to reduce death from cardiovascular causes, but also to reduce the risk of stroke and heart failure hospitalization. This article aims to review and highlight the existing literature on the effects of SGLT-2i, emphasizing their role as oral antihyperglycemic agents in type 2 DM, with important cardiovascular and metabolic benefits.

Critical Care Management of Decompensated Right Heart Failure in Pulmonary Arterial Hypertension Patients - An Ongoing Approach.

Despite substantial advancements in diagnosis and specific medical therapy in pulmonary arterial hypertension patients' management, this condition continues to represent a major cause of mortality worldwide. In pulmonary arterial hypertension, the continuous increase of pulmonary vascular resistance and rapid development of right heart failure determine a poor prognosis. Against targeted therapy, patients inexorable deteriorate over time. Pulmonary arterial hypertension patients with acute right heart failure who need intensive care unit admission present a complexity of the disease pathophysiology. Intensive care management challenges are multifaceted. Awareness of algorithms of right-sided heart failure monitoring in intensive care units, targeted pulmonary hypertension therapies, and recognition of precipitating factors, hemodynamic instability and progressive multisystem organ failure requires a multidisciplinary pulmonary hypertension team. This paper summarizes the management strategies of acute right-sided heart failure in pulmonary arterial hypertension adult cases based on recently available data.

Future perspectives in diabesity treatment: Semaglutide, a glucagon-like peptide 1 receptor agonist (Review).

Given their endemic prevalence in the past decades, obesity and type 2 diabetes mellitus (T2DM) have become a major sanitary burden with an important economic impact. Novel treatment options have been designed with the aim of reducing the numerous complications associated with these metabolic disorders, as well as reducing morbidity and mortality and improving the quality of life of those who suffer from these disorders. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are among the most modern therapeutics that target 'diabesity', a term used to describe the pathophysiological link between obesity and T2DM. Their glucose-lowering effects are mainly attributed to glucose-dependent insulin secretion, glucagon inhibition and decreased gastric emptying. Given the effects on the central nervous system, GLP-1 RA usage may lead to body weight reduction. GLP-1 RAs are classified based on their pharmacokinetic properties as short- and long-acting agents, with both types being administered by subcutaneous injection. The latest agent from this drug class approved for use in T2DM is semaglutide, a long-acting compound that is the only GLP-1 RA available as an oral pill. The present narrative review highlights the most recently published data on the effects and safety of semaglutide in diabetic obesity, also emphasizing its cardiovascular benefits and potential side effects. In addition, an overview of the role of semaglutide in the treatment of non-diabetic obesity is provided.

Short-Term Impact of Iron Deficiency in Different Subsets of Patients with Precapillary Pulmonary Hypertension from an Eastern European Pulmonary Hypertension Referral Center.

BACKGROUND: Over the last few decades, interest in the role of iron status in pulmonary hypertension (PH) has grown considerably due to its potential impact on symptoms, exercise capacity (as assessed by the 6-minute walk distance [6MWD]), prognosis, and mortality. The aim of the present study was to identify iron deficiency (ID) prevalence in specific precapillary PH subgroups of Romanian patients and its short-term impact on 6MWD. PATIENTS AND METHODS: Complete datasets from 25 precapillary PH adults were examined and included in the analysis. Data were collected at baseline and after continuous follow-up of an average of 13.5 months. Enrolled patients were assigned to group 1 (pulmonary arterial hypertension) or subgroup 4.1 (chronic thromboembolic pulmonary hypertension), and individualized targeted therapy was prescribed. General characteristics, World Health Organization functional class, 6MWD, pulse oximetry, laboratory parameters, and echocardiographic and hemodynamic parameters were recorded. Ferritin values and transferrin saturation were used to assess ID. RESULTS: At baseline, 16 out of 25 patients were iron deficient. The univariate linear regression analysis did not show a statistically significant impact of ID on 6MWD (p=0.428). In multivariate regression analysis, possible predictors of 6MWD, including ID, were not statistically significant at baseline or after an average of 13.5 months follow-up (p=0.438, 0.361, respectively) and ID indicates a negative impact on 6MWD independent of applied corrections. CONCLUSION: The results of this study demonstrate that 1.4.1 subgroup PAH patients have an increased prevalence of ID compared with other etiologies. ID has a negative impact on the functional status (assessed by 6MWD), in specific groups and subgroups of patients with precapillary PH, albeit not independently nor significant to other known predictors such as age, gender, oxygen saturation, and hemoglobin value. These data can be integrated with global research and are consistent with phenotypes of patients diagnosed with PH of different etiologies.

Native Aortic Valve Endocarditis Complicated by Splenic Infarction and Giant Mitral-Aortic Intervalvular Fibrosa Pseudoaneurysm-A Case Report and Brief Review of the Literature.

BACKGROUND: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is an unusual complication related to various injuries or conditions which involve the mitro-aortic region; it communicates with the left ventricular outflow tract and is associated with a high-risk of redoubtable complications or sudden death. The cerebral and splenic localizations are frequently seen as manifestations of systemic embolism in infective endocarditis. Currently, there are no specific recommendations related to the diagnosis, management, treatment, or further evolution of patients with P-MAIVF and concomitant splenic infarction. This paper presents the case of a 43-year-old Caucasian woman with a late diagnosis of mixed bicuspid aortic valve disease, affected by an under-detected and undertreated episode of infective endocarditis leading to asymptomatic P-MAIVF. Prime clinical and imagistic diagnosis of splenic infarction indicated further extended investigations were required to clarify the source of embolism. METHODS: Integrated multimodality imaging techniques confirmed the unexpected diagnosis of P-MAIVF. RESULTS: The case had a fatal outcome following an uncomplicated yet laborious cardiac surgery. Patient death was attributed to a malignant ventricular arrhythmia. CONCLUSION: The present case raises awareness by highlighting an unexplained and unexpected splenic infarction association with P-MAIVF as a result of infective endocarditis related to mixed bicuspid aortic valve disease.

Cardiovascular Events throughout the Disease Course in Chronic Myeloid Leukaemia Patients Treated with Tyrosine Kinase Inhibitors-A Single-Centre Retrospective Study.

INTRODUCTION: Cardiovascular risk factors, pre-existing comorbidities, molecular factors, and the direct effects of second- and third-generation BCR-ABL1 tyrosine kinase inhibitors on the vascular endothelium contribute to the progression of cardiovascular (CV) events, especially atherothrombotic conditions. The study objective was to evaluate comorbidities, the cardiovascular risk profile, and events throughout the chronic myeloid leukaemia disease course. METHODS: Retrospective data from adults who experienced haematology treatment at a single centre were continuously updated and followed throughout the disease course. A total of 43 subjects conforming with the inclusion and exclusion criteria of the study protocol were finally recruited. The median disease course was 77.0 ± 17.5 months. Statistical analyses were performed. RESULTS: More than three CV risk factors were identified in 41.9% of cases. Almost half of the cases had relevant comorbidities (Charlson Comorbidity Index (CCI) ≥ 4), and no statistically significant comorbidities were found when comparing the tyrosine kinase inhibitor (TKI) treatment subgroups (p = 0.53). The patients at high and very high CV risk, according to Systematic Coronary Risk Evaluation (SCORE) risk classification, had 75.0% CV events (12/22 patients), p = 0.45. Throughout the disease course, 19 cardiovascular events were reported in 37.2% patients (13 males/3 females, p < 0.03). CONCLUSION: To the best of our knowledge, this is the first study exploring cardiovascular risk factors in Romanian chronic myeloid leukaemia patients. This study reinforces the need for close long-term follow-up that should be performed by a multidisciplinary team. The target should be not only the disease and specific drug-related toxicities but, also, the identification of cardiovascular and metabolic risk factors before the commencement of and throughout TKI therapy.