Systemic lupus erythematosus: one year in review 2024.

Systemic lupus erythematosus (SLE) is classically regarded as the landmark of systemic autoimmune diseases, characterised by protean, multi-systemic manifestations and a highly variable clinical course.Over the last years, both clinical and translational clinical research efforts led to significant steps forward in management and treatment of SLE. However, numerous aspects of SLE, from pathogenesis to treatment, still remain challenging, and several unmet needs persist for both patients and physicians. Following the previous annual reviews of this series, herewith, we aim to report the most relevant new updates on SLE, issued in 2023. In particular, we focused on biomarkers, clinical aspects and outcomes, comorbidities, as well as new treatment targets and real-world evidence.

New Frontiers in Pancreatic Cancer Management: Current Treatment Options and the Emerging Role of Neoadjuvant Therapy.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the 15 most prevalent cancers globally, characterized by aggressive growth and late-stage diagnosis. Advances in imaging and surgical techniques have redefined the classification of pancreatic PDAC into resectable, borderline resectable, and locally advanced pancreatic cancer. While surgery remains the most effective treatment, only 20% of patients are eligible at diagnosis, necessitating innovative strategies to improve outcomes. Therefore, traditional treatment paradigms, primarily surgical resection for eligible patients, are increasingly supplemented by neoadjuvant therapies (NAT), which include chemotherapy, radiotherapy, or a combination of both. By administering systemic therapy prior to surgery, NAT aims to reduce tumor size and increase the feasibility of complete surgical resection, thus enhancing overall survival rates and potentially allowing more patients to undergo curative surgeries. Recent advances in treatment protocols, such as FOLFIRINOX and gemcitabine-nab-paclitaxel, now integral to NAT strategies, have shown promising results in increasing the proportion of patients eligible for surgery by effectively reducing tumor size and addressing micrometastatic disease. Additionally, they offer improved response rates and survival benefits compared to traditional regimes. Despite these advancements, the role of NAT continues to evolve, necessitating ongoing research to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from these approaches. Through a detailed analysis of current literature and recent clinical trials, this review highlights the transformative potential of NAT in managing PDAC, especially in patients with borderline resectable or locally advanced stages, promising a shift towards more personalized and effective management strategies for PDAC.

Systemic lupus erythematosus: one year in review 2023.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. New data regarding pathogenic pathways, biomarkers and clinical manifestations of SLE are emerging, and new drugs and therapeutic protocols have been proposed to improve the control of disease activity. Furthermore, new insights into comorbidities and reproductive health in SLE patients are constantly emerging.This annual review aims to summarise the most relevant data on SLE that was published in 2022.

One year in review 2022: systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multisystem auto-immune disease with extremely varied clinical manifestations and a complex pathogenesis. New insights in SLE about pathogenetic pathways, biomarkers, and data on clinical manifestations are progressively emerging, and new drugs and new therapeutic strategies have been proposed to improve the control of disease activity. Thus, this review is aimed to summarise the most relevant data about SLE emerged during 2021, following the previous annual review of this series.

Pressure ulcers in cardiac surgery: Few clinical studies, difficult risk assessment, and profound clinical implications.

Pressure ulcers (PUs) are a common complication after cardiac surgery, with almost one third of patients suffering from PUs during hospitalisation. Because of the burden that PUs exert on both the patients and the health care system, prevention is of utmost importance. The first step in successful prevention, however, includes the identification of the main features that render patients prone to PU development. Cardiac surgery population is not adequately addressed in current clinical trials and studies. Few studies focused specifically on cardiac surgery patients, but the majority included cardiac surgery patients within a heterogeneous population of acute or critical care patients. Therefore, additional research is warranted to understand the unique risk profile of patients undergoing cardiac surgery. Intraoperative risk factors that affect tissue tolerance have not been thoroughly investigated but are likely to play an important role, which might explain the epidemiology of a PU. Further research is also needed to better comprehend the risk of PUs among cardiac surgery patients and to design effective and tailored preventative measures with the help of newer tools for risk assessment.

Textbook Outcomes in Solid Transplantation: A Systematic Review.

Background: The concept of TO is expanding across various surgical disciplines to establish a standardized, comprehensive quality benchmark. Traditional metrics such as 1-y patient and graft survival have been key for evaluating transplant program performance but are now deemed inadequate because of significant field advancements. This systematic review aims to provide a comprehensive understanding of the applicability and validity of textbook outcome (TO) in the setting of solid organ transplantation. Methods: A structured search, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, was conducted across PubMed, Embase, and Scopus databases on March 10, 2024. Results: Fourteen articles were identified for inclusion in this review. Of these, 2 studies addressed TO in heart transplantation, 3 in lung transplantation, 2 in kidney transplantation, and 7 in liver transplantation. A subgroup analysis was conducted to categorize the different definitions of TOs and identify the most common reasons for TO failure. Conclusions: Our systematic review highlights the ongoing efforts in the field of solid organ transplantation to define TO and emphasizes the importance of developing a universally recognized set of TO criteria for each type of transplant. TO provides a valuable framework for transplant centers to benchmark their performance against similar institutions on a risk-adjusted basis and to pinpoint specific areas for enhancing patient outcomes. Even the most successful programs may discover aspects within the composite outcome with scope for improvement.

Robotic Vascular Resection in Pancreatic Ductal Adenocarcinoma: A Systematic Review.

(1) Background: This study comprehensively compared robotic pancreatic surgery with vascular resection (RPS-VR) to other surgical procedures in the treatment of pancreatic ductal adenocarcinoma (PDAC). (2) Methods: A systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes. (3) Results: Findings indicate that robotic surgery with vascular resections (VRs) significantly prolongs the duration of surgery compared to other surgical procedures, and they notably demonstrate an equal hospital stay. While some studies reported a lower conversion rate and a higher rate of blood loss and blood transfusion in the RPS-VR group, others found no significant disparity. Furthermore, RPS-VR consistently correlated with comparable recurrence rates, free margins R0, postoperative mortality, and complication rates. Concerning the last one, certain reviews reported a higher rate of major complications. Overall survival and disease-free survival remained comparable between the RPS-VR and other surgical techniques in treating PDAC. (4) Conclusions: The analysis emphasizes how RPS-VR is a resembling approach in terms of surgical outcomes and aligns with existing literature findings in this field.

Impact of disease activity patterns on health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE).

OBJECTIVE: To assess the impact of different disease activity patterns-long quiescent (LQ), chronically active (CA) and relapsing-remitting (RR)-on health-related quality of life (HRQoL) in a cohort of patients with systemic lupus erythematosus (SLE). METHODS: A retrospective, monocentric analysis of prospectively collected data. Adult SLE outpatients were enrolled between 2017 and 2021.For each year of follow-up, three disease activity patterns were defined: LQ if at each visit clinical Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Activity Index (SELENA-SLEDAI)=0, Physician Global Assessment (PGA)=0; CA if at each visit clinical SELENA-SLEDAI >0, PGA >0; RR if patients presented active disease in at least one visit during the observation period, interspersed with periods of remission. These patterns were applied to the year and the 3 years before enrolment.At enrolment, each patient completed: Short Form 36 (SF-36), Lupus Impact Tracker, Functional Assessment of Chronic Illness Therapy (FACIT), Hospital Anxiety and Depression Scale (HADS). The correlation between disease patterns and Patient-Reported Outcomes was analysed. RESULTS: 241 SLE patients were enrolled, of which 222 had complete clinical data for the 3-year period before enrolment. Both in the year and during the 3 years before enrolment, the most frequent disease pattern was the LQ (154/241 and 122/222 patients, respectively), followed by RR (53/241 and 92/222 patients, respectively) and CA (34/241 and 8/222 patients, respectively).At baseline, fibromyalgia, organ damage, age and daily glucocorticoid dose were associated with worse HRQoL.At the multivariable analysis, after adjusting for confounding factors, patients with LQ disease during the 3 years before enrolment presented a better physical HRQoL (SF-36 physical component summary, regression coefficient=3.2, 95% CI 0.51-5.89, p=0.02) and minor depressive symptoms (HADS-D, regression coefficient=-1.17, 95% CI -2.38 to 0.0.27, p=0.055), compared with patients with CA/RR disease. CONCLUSION: A persistently quiescent disease may have a positive impact on patients' physical HRQoL and on depressive symptoms. However, this condition appears insufficient to obtain a significant improvement in mental health, fatigue and disease burden among patients with SLE.

Analysis of belimumab prescription and outcomes in a 10-year monocentric cohort: is there an advantage with early use?

OBJECTIVE: The objective is to evaluate perscriptions of belimumab (BEL), how these have changed over the years and their impact on clinical outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This is a retrospective analysis of prospectively collected data. We retrieved demographic and clinical data and concomitant therapies at BEL starting (baseline). Disease activity was assessed at baseline and after 6 and 12 months and organ damage at baseline and at the last visit. RESULTS: From 422 patients followed in the Pisa SLE cohort, 102 patients received BEL and were included and 22 (21.6%) were immunosuppressant (IS)-naïve. Lupus Low Disease Activity State (LLDAS) with a glucocorticoid (GC) dosage ≤5 mg/day (LLDAS5) and remission were achieved by 47% and 38% of patients at 6 months, and by 75% and 66% at 12 months. Comparing IS-naïve patients with those who received BEL after at least one conventional IS, we did not find significant differences in baseline characteristics and in the achievement of LLDAS5 and remission. Despite at baseline we did not observe significant differences in mean GC daily dosage, IS-naïve patients were taking a significantly lower GC daily dose at 6 and 12 months. Interestingly, IS-naïve patients were more common in the most recent years. CONCLUSIONS: Our data confirm that BEL is effective in controlling disease activity, and in recent years BEL has been considered as an earlier treatment option before other IS. Early introduction of BEL can be at least as effective as a step-up approach and can help to reduce the GC dosage.

Gender differences in SLE: report from a cohort of 417 Caucasian patients.

BACKGROUND: SLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course, drug response and damage accrual is yet to be fully explored and comprehended. OBJECTIVES: To describe gender differences in disease course, comorbidities, use of medications and long-term outcomes of a large cohort of patients with SLE. METHODS: Retrospective gender-based analysis of prospectively collected data from a monocentric cohort of Caucasian patients with SLE with at least 1 year of follow-up. RESULTS: 417 patients were included, 51 men and 366 women. Men displayed a significantly higher median age at disease onset and diagnosis and a higher prevalence of late-onset SLE, serositis at disease onset, antiphospholipid syndrome (APS) and use of mycophenolate within the first year of disease. Women had a higher prevalence of haematological abnormalities, a higher cumulative exposure to azathioprine and higher cumulative dose of glucocorticoids at 5 years. Male patients had a shorter time to first damage item and a higher prevalence of damage at 1 and 5 years, but this association was no longer significant when late-onset patients were excluded. No differences were found in prevalence of childhood onset, delay between onset and diagnosis, time to renal involvement and histology, cumulative autoantibody positivity, number of flares and hospitalisations, median SLE Damage Index score, type of damage, age and time to first cardiovascular event, chronic kidney disease and death. CONCLUSIONS: In our cohort, clinical manifestations and disease course were similar in male and female patients; however, male patients displayed higher prevalence of APS and early damage accrual probably due to the later disease onset. These data highlight the importance of an intensive follow-up, prevention and treatment of complications in this category of patients, especially in the first years of disease.

Effect of Statins on Platelet Activation and Function: From Molecular Pathways to Clinical Effects.

PURPOSE: Statins are a class of drugs widely used in clinical practice for their lipid-lowering and pleiotropic effects. In recent years, a correlation between statins and platelet function has been unveiled in the literature that might introduce new therapeutic indications for this class of drugs. This review is aimed at summarizing the mechanisms underlying statin-platelet interaction in the cardiologic scenario and building the basis for future in-depth studies. METHODS: We conducted a literature search through PubMed, Embase, EBSCO, Cochrane Database of Systematic Reviews, and Web of Science from their inception to June 2020. RESULTS: Many pathways could explain the interaction between statins and platelets, but the specific effect depends on the specific compound. Some could be mediated by enzymes that allow the entry of drugs into the cell (OATP2B1) and others by enzymes that mediate their activation (PLA2, MAPK, TAX2, PPARs, AKT, and COX-1), recruitment and adhesion (LOX-1, CD36, and CD40L), or apoptosis (BCL2). Statins also appear to have a synergistic effect with aspirin and low molecular weight heparins. Surprisingly, they seem to have an antagonistic effect with clopidogrel. CONCLUSION: There are many pathways potentially responsible for the interactions between statins and platelets. Their effect appears to be closely related, and each single effect can be barely measured. Also, the same compound might have complex downstream signaling with potentially opposite effects, i.e., beneficial or deleterious. The multiple clinical implications that can be derived as a result of this interaction, however, represent an excellent reason to develop future in-depth studies.