Advances in the pharmacological management of cutaneous T-cell lymphoma.

INTRODUCTION: Current treatment guidelines for cutaneous T cell lymphoma (CTCL) advocate a stage-driven approach, considering clinical presentation, symptom burden, and patient comorbidities. Therapy selection hinges on factors like disease subtype, severity, and treatment availability. The primary goal is to enhance the quality of life by mitigating symptoms, as achieving lasting complete remission is infrequent. AREAS COVERED: Over the past decade (2013-2023), the therapeutic landscape of CTCL has experienced substantial transformation with the introduction of innovative therapies. This review explores the main pivotal developments in traditional treatment schedules and recently introduced drugs, aiming to offer clinicians and researchers a thorough perspective on the decade's progress in the field. EXPERT OPINION: Despite the progress made in CTCL therapeutics, ranging from topical chemotherapeutics to immunomodulatory agents, several unmet needs persist. Firstly, there is a pressing need for the incorporation of readily available predictors for treatment response, encompassing clinical, pathological, and molecular features. Secondly, a more profound comprehension of the tumor microenvironment is imperative to optimize the landscape of targetable molecules. Lastly, the undertaking of studies on combination regimens should be encouraged as it enhances therapy efficacies by synergistically combining agents with diverse modes of action.

Emerging prognostic biomarkers in advanced cutaneous melanoma: a literature update.

INTRODUCTION: Over the past two years, the scientific community has witnessed an exponential growth in research focused on identifying prognostic biomarkers for melanoma, both in pre-clinical and clinical settings. This surge in studies reflects the need of developing effective prognostic indicators in the field of melanoma. AREAS COVERED: The aim of this work is to review the scientific literature on the most recent findings on the development or validation of prognostic biomarkers in melanoma, in the attempt of providing both clinicians and researchers with an updated broad synopsis of prognostic biomarkers in cutaneous melanoma. EXPERT OPINION: While the field of prognostic biomarkers in melanoma appears promising, there are several complexities and limitations to address. The interdependence of clinical, histological, and molecular features requires accurate classification of different biomarker families. Correlation does not imply causation, and adjustments for confounding factors are often overlooked. In this scenario, large-scale studies based on high-quality clinical trial data can provide more reliable evidence. It is essential to avoid oversimplification by focusing on a single biomarker, as the interactions among multiple factors contribute to define the disease course and patient's outcome. Furthermore, implementing well-supported evidence in real-life settings can help advance prognostic biomarker research in melanoma.

Pathophysiology and Therapy of High-Altitude Sickness: Practical Approach in Emergency and Critical Care.

High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.

CD157 signaling promotes survival of acute myeloid leukemia cells and modulates sensitivity to cytarabine through regulation of anti-apoptotic Mcl-1.

CD157/BST-1 (a member of the ADP-ribosyl cyclase family) is expressed at variable levels in 97% of patients with acute myeloid leukemia (AML), and is currently under investigation as a target for antibody-based immunotherapy. We used peripheral blood and bone marrow samples from patients with AML to analyse the impact of CD157-directed antibodies in AML survival and in response to cytarabine (AraC) ex vivo. The study was extended to the U937, THP1 and OCI-AML3 AML cell lines of which we engineered CD157-low versions by shRNA knockdown. CD157-targeting antibodies enhanced survival, decreased apoptosis and reduced AraC toxicity in AML blasts and cell lines. CD157 signaling activated the PI3K/AKT/mTOR and MAPK/ERK pathways and increased expression of Mcl-1 and Bcl-XL anti-apoptotic proteins, while decreasing expression of Bax pro-apoptotic protein, thus preventing Caspase-3 activation. The primary CD157-mediated anti-apoptotic mechanism was Bak sequestration by Mcl-1. Indeed, the Mcl-1-specific inhibitor S63845 restored apoptosis by disrupting the interaction of Mcl-1 with Bim and Bak and significantly increased AraC toxicity in CD157-high but not in CD157-low AML cells. This study provides a new role for CD157 in AML cell survival, and indicates a potential role of CD157 as a predictive marker of response to therapies exploiting Mcl-1 pharmacological inhibition.

Psychopathology, personality and theory of mind in a sample of university students.

OBJECTIVE: To assess psychopathology, personality and theory of mind in a sample of university students, and to analyse their correlation with socio-demographic and academic factors. MATERIALS AND METHODS: Socio-demographic and academic data were collected from 228 students. They completed the Eysenck Personality Questionnaire-R, Symptom Checklist-90-R (SCL-90-L) and Theory of Mind (ToM) test. RESULTS: Elevated psychological distress was found in 38.6% of students; 30.3% had an abnormal ToM score. Students with an abnormal ToM score had a significantly lower probability than those with normal ToM test to repeat an exam three times or more. Not being married and receiving psychiatric care significantly influenced the probability of repeating an exam. Abnormal ToM students had specific features as far as major and SCL-90-R scores are concerned. CONCLUSIONS: A correlation was found among ToM performance and some indicators of academic performance. Students with ToM scores under the cut-off reported more psychopathological symptoms and distress. Implications are discussed

A cluster randomized trial to assess the effect of clinical pathways for patients with stroke: results of the clinical pathways for effective and appropriate care study.

BACKGROUND: Clinical pathways (CPs) are used to improve the outcomes of acute stroke, but their use in stroke care is questionable, because the evidence on their effectiveness is still inconclusive. The objective of this study was to evaluate whether CPs improve the outcomes and the quality of care provided to patients after acute ischemic stroke. METHODS: This was a multicentre cluster-randomized trial, in which 14 hospitals were randomized to the CP arm or to the non intervention/usual care (UC) arm. Healthcare workers in the CP arm received 3 days of training in quality improvement of CPs and in use of a standardized package including information on evidence-based key interventions and indicators. Healthcare workers in the usual-care arm followed their standard procedures. The teams in the CP arm developed their CPs over a 6-month period. The primary end point was mortality. Secondary end points were: use of diagnostic and therapeutic procedures, implementation of organized care, length of stay, re-admission and institutionalization rates after discharge, dependency levels, and complication rates. RESULTS: Compared with the patients in the UC arm, the patients in the CP arm had a significantly lower risk of mortality at 7 days (OR = 0.10; 95% CI 0.01 to 0.95) and significantly lower rates of adverse functional outcomes, expressed as the odds of not returning to pre-stroke functioning in their daily life (OR = 0.42; 95 CI 0.18 to 0.98). There was no significant effect on 30-day mortality. Compared with the UC arm, the hospital diagnostic and therapeutic procedures were performed more appropriately in the CP arm, and the evidence-based key interventions and organized care were more applied in the CP arm. CONCLUSIONS: CPs can significantly improve the outcomes of patients with ischemic patients with stroke, indicating better application of evidence-based key interventions and of diagnostic and therapeutic procedures. This study tested a new hypothesis and provided evidence on how CPs can work. TRIAL REGISTRATION: ClinicalTrials.gov ID: [NCT00673491].

Effect of introducing a care pathway to standardize treatment and nursing of schizophrenia.

Care pathways can help to implement evidence-based clinical practice. The introduction of care pathways is difficult for psychiatric disorders. This study examined whether the organization and the effectiveness of care provided to schizophrenic patients can be improved by care pathways. Outcomes from 19 patients receiving treatment using evidence-based care pathways were compared with 17 patients receiving a traditional approach to care over a 3 months period. Results showed significant improvements in the quality of the care for the patients included in the care pathway group. The authors concluded the positive outcomes for patients treated with care pathways were related to the assistance provided to clinicians in identifying and implementing evidence-based standards.

A cluster randomized trial to assess the impact of clinical pathways for patients with stroke: rationale and design of the Clinical Pathways for Effective and Appropriate Care Study [NCT00673491].

BACKGROUND: Patients with stroke should have access to a continuum of care from organized stroke units in the acute phase, to appropriate rehabilitation and secondary prevention measures. Moreover to improve the outcomes for acute stroke patients from an organizational perspective, the use of multidisciplinary teams and the delivery of continuous stroke education both to the professionals and to the public, and the implementation of evidence-based stroke care are recommended. Clinical pathways are complex interventions that can be used for this purpose. However in stroke care the use of clinical pathways remains questionable because little prospective controlled data has demonstrated their effectiveness. The purpose of this study is to determine whether clinical pathways could improve the quality of the care provided to the patients affected by stroke in hospital and through the continuum of the care. METHODS: Two-arm, cluster-randomized trial with hospitals and rehabilitation long-term care facilities as randomization units. 14 units will be randomized either to arm 1 (clinical pathway) or to arm 2 (no intervention, usual care). The sample will include 238 in each group, this gives a power of 80%, at 5% significance level. The primary outcome measure is 30-days mortality. The impact of the clinical pathways along the continuum of care will also be analyzed by comparing the length of hospital stay, the hospital re-admissions rates, the institutionalization rates after hospital discharge, the patients' dependency levels, and complication rates. The quality of the care provided to the patients will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and rehabilitation, and by the use of key quality indicators at discharge. The implementation of organized care will be also evaluated. CONCLUSION: The management of patients affected by stroke involves the expertise of several professionals, which can result in poor coordination or inefficiencies in patient treatment, and clinical pathways can significantly improve the outcomes of these patients. It is proposed that this study will test a new hypothesis and provide evidence of how clinical pathways can work. TRIAL REGISTRATION: ClinicalTrials.gov ID [NCT00673491].

A cluster randomized controlled trial of a clinical pathway for hospital treatment of heart failure: study design and population.

BACKGROUND: The hospital treatment of heart failure frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality and economic cost of this disorder. Consequently the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. Despite enthusiasm and diffusion, the widespread acceptance of clinical pathways remain questionable because very little prospective controlled data demonstrated their effectiveness. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was designed in order to conduct a rigorous evaluation of clinical pathways in hospital treatment of acute heart failure. The primary objective of the trial was to evaluate the effectiveness of the implementation of clinical pathways for hospital treatment of heart failure in Italian hospitals. METHODS/DESIGN: Two-arm, cluster-randomized trial. 14 community hospitals were randomized either to arm 1 (clinical pathway: appropriate use of practice guidelines and supplies of drugs and ancillary services, new organization and procedures, patient education, etc.) or to arm 2 (no intervention, usual care). 424 patients sample (212 in each group), 80% of power at the 5% significance level (two-sided). The primary outcome measure is in-hospital mortality. We will also analyze the impact of the clinical pathways comparing the length and the appropriateness of the stay, the rate of unscheduled readmissions, the customers' satisfaction and the costs treating the patients with the pathways and with the current practice along all the observation period. The quality of the care will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and by measuring key quality indicators at discharge. DISCUSSION: This paper examines the design of the evaluation of a complex intervention. Since clinical pathways are made up of various interconnecting parts we have chosen the cluster-randomized controlled trial because is widely accepted as the most reliable method of determining effectiveness when measuring cost-effectiveness in real practice. TRIAL REGISTRATION: ClinicalTrials.gov ID [NCT00519038].

Care pathways in obstetrics: the effectiveness in reducing the incidence of episiotomy in childbirth.

AIM: To develop a care pathway for childbirth. BACKGROUND: Care pathways are emerging as an effective tool to improve clinical and organizational performance. METHODS: A pre- and postimplementation analysis model was used to evaluate the effect of introducing a care pathway for childbirth. Key outcome indicators and costs were reviewed to compare the traditional care processes with those of the care pathway. The study involved 380 women. RESULTS: There was a significant reduction in episiotomy rate (from 14.90% to 8.6%, P = 0.02) in patients being cared for using a care pathway approach; however, there were no differences in caesarean section and in perineal wound rates. The average costs per patient on the care pathway were euro 1278.42 ( pound 873.64) compared with euro 1,146.87 ( pound 783.74) preimplementation. The study also demon- strated an increase in patient satisfaction for women cared for using the care pathway approach. CONCLUSIONS: The care pathway proved to be a valid methodological approach to childbirth, allowing healthcare workers to efficiently share the care of the women, guaranteeing safe and effective care.

[Study on the appropriateness of utilization of dermatological consultants in emergency unit]. / Appropriatezza delle richieste di consulenza dermatologica in Pronto Soccorso in una Azienda Ospedaliera piemontese.

The aim of this study is to evaluate the rate of appropriate use of dermatologist consultants, in order to identify its determinants and to define its economic impact. We analysed 1750 dermatological procedures performed in the emergency room of the Azienda Ospedaliera "Maggiore della Carità" in Novara. The 87,64% of the procedures were inappropriate. We also observed low rates of diagnostic agreement between emergency unit and dermatology unit; 40.88% of discordant diagnoses were due to severe mistakes. The rate of inappropriate dermatological procedures was related to the clinical diagnosis and to patient's access time. The economical analysis was performed using the Activity Based Costing methodology. We measured an average expenditure of euro 7 for procedure (total expenditure euro 9.850). As possible determinants of inappropriateness, we identified the lack of "filter action" by general practitioners, the incorrect behaviour of patients and the professional uncertainty phenomena.