The burden of pre-operative anaemia and postoperative outcomes in 15 166 surgical patients from a public hospital in Brazil: A retrospective cohort study.

BACKGROUND: Preoperative anaemia is associated with poor postoperative outcomes; however, few studies have reported its prevalence in developing countries and its association with significant postoperative outcomes. OBJECTIVE: We aimed to identify the prevalence of anaemia and its association with postoperative outcomes in a major public hospital in Brazil. DESIGN: Retrospective cohort study. SETTING: Single-centre, 860-bed, quaternary university-affiliated teaching hospital in Southern Brazil. PATIENTS: We included adult patients who had undergone surgery between 2015 and 2019. Main outcome measures: The main outcome was the in-hospital 30-day postoperative mortality. According to the World Health Organisation, we defined anaemia and its sub-classification (mild, moderate, and severe). We developed Poisson regression models to examine the association between preoperative anaemia and outcomes. RESULTS: We included 15 166 patients, of whom 6387 (42.1%) were anaemic. After adjustment for confounding factors, patients with anaemia had an increased risk of in-hospital 30-day postoperative mortality (relative risk (RR) 1.69, 95% confidence interval (CI) 1.44 to 1.99, P < 0.001). Mild [relative risk (RR) 1.38, 95% CI 1.12 to 1.71, P = 0.003], moderate (RR 1.73, 95% CI 1.43 to 2.10, P < 0.001), and severe anaemia (RR 2.43, 95% CI 1.92 to 3.07, P < 0.001) were associated with the primary outcome. Anaemia increased the transfusion risk (RR 4.44, 95% CI 3.90 to 5.06, P < 0.001) and postoperative intensive care unit (ICU) admission (RR 1.09, 95% CI 1.04 to 1.16, P = 0.001). CONCLUSIONS: Four out of 10 patients had anaemia. These patients had an increased risk of adverse postoperative outcomes. Comprehension of the magnitude and impact of anaemia is essential to establish interventions in low-resource scenarios to optimise the patient's journey. STUDY REGISTRATION: Institutional Review Board Registration number 40522820000005327 (Brazilian CEP/CONEP System, available in https://plataformabrasil.saude.gov.br/).

Subclinical left ventricular dysfunction in rheumatoid arthritis: findings from the prospective Porto-RA cohort.

AIM: Patients with rheumatoid arthritis (RA) have an increased risk of cardiac dysfunction and heart failure (HF) due to a pro-inflammatory state. Detecting cardiac dysfunction in RA is challenging as these patients often present preserved ejection fraction (EF) but may have subclinical ventricular dysfunction. Echocardiographic strain analysis is a promising tool for early detection of subclinical left ventricular systolic dysfunction (LVSD). This study assesses the prognostic role of strain analysis in RA. METHODS AND RESULTS: Prospective study of 277 RA patients without known heart disease and preserved EF, categorized by left ventricular global longitudinal strain (GLS): normal GLS (≤ - 18%) vs. subclinical LVSD (> - 18%). Primary outcome was a composite of myocardial infarction, HF hospitalization, stroke, or cardiovascular death (MACE). Mean age was 57 years, 79% female. Although mean GLS was within normal (- 20 ± 3%), subclinical LVSD was observed in 24% of patients (n = 67) and was positively correlated with older age (OR 1.54 per 10 years; p < 0.001) and comorbid conditions, such as dyslipidemia (OR 2.27; p = 0.004), obesity (OR 2.29; p = 0.015), and chronic kidney disease (OR 8.39; p = 0.012). Subclinical LVSD was independently associated with a 3.9-fold higher risk of MACE (p = 0.003) and a 3.4-fold higher risk of HF hospitalization/cardiovascular death (p = 0.041). A GLS threshold of > - 18.5% provided optimal sensitivity (78%) and specificity (74%) in identifying patients at elevated MACE risk (AUC = 0.78; p < 0.001). CONCLUSION: Subclinical LVSD, identified by reduced GLS, was strongly associated with adverse cardiovascular events in RA. Whether these findings have therapeutic implications is worth exploring in clinical trials.

What Does N2 Lymph Node Involvement Mean for Patients with Non-Small Cell Lung Cancer (NSCLC)?-A Review of Implications for Diagnosis and Treatment.

Patients with stage III NSCLC with N2 lymph node involvement carry a complex and diverse disease entity. Challenges persist in the areas of diagnosis, staging, multimodal management, and the determination of surgical indications and resectability criteria. Therefore, this review focuses on the latest updates in N2 disease staging and its prognostic and treatment implications. Emphasis is placed on the importance of accurate staging using imaging modalities such as [18F]FDG-PET/CT as well as minimally invasive mediastinal staging endoscopic techniques. The evolving role of surgery in the management of N2 disease is also explored. The benefits of neoadjuvant and adjuvant treatments have been demonstrated, along with the efficacy of a combined multimodal approach with chemo-immunotherapy in the perioperative setting, reigniting the debate of N2 disease subsets and optimal treatment options. Furthermore, this review addresses the controversies surrounding surgical approaches in upfront "borderline" resectable stage III NSCLC as well as the benefits of combined chemoradiotherapy with consolidation immunotherapy for patients with unresectable tumors. In conclusion, personalized diagnostic and treatment approaches tailored to individual patient characteristics, resource availability, and institutional expertise are essential for optimizing outcomes in patients with stage III-N2 NSCLC.

Impact of right ventricle-pulmonary artery coupling in patients undergoing transcatheter aortic valve implantation.

Right ventricle-pulmonary artery (RV-PA) coupling has been linked to clinical outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter valve implantation (TAVI). However, the best timing for prognostic assessment remains uncertain. Our aim was to determine the impact of RV longitudinal function parameters and RV-PA coupling on mortality in patients undergoing TAVI.  Retrospective, single center, analysis including patients with AS who underwent TAVI between 2007 and 2021. Echocardiographic evaluation was performed before, shortly after the procedure, and during follow-up. RV-PA uncoupling was defined as a TAPSE/PASP ratio<0.55 (severe RV uncoupling was defined as TAPSE/PASP ratio<0.32. The effect of RV parameters on all-cause mortality up to 12 months was assessed.  Among the 577 patients included, pre-procedural TAPSE/PASP ratio data were available for 205. RV-PA uncoupling was present in 113 patients (55.1%), with severe uncoupling observed in 31 (15.1%). Within the first 12 months after TAVI, 51 patients (9%) died. Severe RV-PA uncoupling was associated with mortality in univariable Cox regression; however, this association was lost after adjusting for EuroSCORE II. A significant association was found between the TAPSE/PASP ratio (per 0.1-unit increase) after the procedure and the primary endpoint (HR: 0.73; 95% CI: 0.56, 0.97; p=0.029). Higher postprocedural PASP (HR: 1.04; 95% CI: 1.02, 1.06; p<0.001 was also associated with all-cause mortality.  V-PA uncoupling and PASP after TAVI are associated with all-cause mortality in patients and may be valuable for patient selection and for planning post-procedural care.

Twelve-year trends in unprotected left main coronary artery occlusion: insights from a real-world multicentre study.

AIMS: Acute myocardial infarction (AMI) resulting from unprotected left main coronary artery (LMCA) occlusion and subtotal occlusion is a life-threatening condition. Although AMI management has improved in the past two decades, there is limited information on recent trends in patient characteristics, management, and outcomes for acute unprotected LMCA-related AMI. This study aims to assess such trends over a 12 year period. METHODS AND RESULTS: This retrospective multicentre study includes patients with unprotected LMCA occlusion/subtotal occlusion admitted to three tertiary hospitals between 2008 and 2020. The patients were divided into two groups based on the chronology of presentation: a 'past group' (January 2008 to December 2014) and a 'contemporary group' (January 2015 to December 2020). The study compares clinical characteristics, management approaches, and outcomes between the two groups. The study includes 128 patients, with 51 (40%) in the 'past group' and 77 (60%) in the 'contemporary group'. Baseline risk factors did not show statistically significant differences between the two groups, except for hypertension (49% vs. 74%; P = 0.005). Chest pain was more frequent in the 'past group' (98% vs. 89%; P = 0.014), and a trend towards more cardiac arrests was observed in the 'contemporary group' (18% vs. 31%; P = 0.087). Revascularization type did not differ significantly (P = 0.419), but manual thrombectomy was less frequently used (41% vs. 23%; P = 0.032) and stent implantation showed a trend towards higher rates (66% vs. 78%; P = 0.150) in the 'contemporary cohort'. There was a gradual shift from bare-metal to drug-eluting stents, with a significantly higher percentage of ticagrelor/prasugrel loading in the 'contemporary cohort' (5% vs. 79%; P < 0.001). The use of mechanical circulatory support (MCS), although not statistically significant, was higher among patients in the 'past group' (67% vs. 51%; P = 0.073). The type of MCS differed significantly between groups, with a decrease in intra-aortic balloon pump use (67% vs. 42%; P = 0.005) and an increase in veno-arterial extracorporeal membrane oxygenation (4% vs. 22%; P = 0.005) and Impella system (0% vs. 3%) over time. Survival analysis showed no significant differences (P = 0.599; log-rank test) in all-cause mortality between the different time groups, with the long-term survival rate being approximately 30%. CONCLUSIONS: In our real-world population, despite the progressive use of newer drugs and more advanced devices over time, patients with unprotected LMCA occlusion/subtotal occlusion remain a subpopulation with poor prognosis.

Cervical cancer in Mozambique: Clinical characteristics, treatment and survival of incident cases admitted to the Oncology Service of Maputo Central Hospital in 2016-2018.

In Mozambique, cervical cancer is the most frequent cancer in women. However, studies about cervical cancer treatment and prognosis are scarce. We describe the clinical characteristics, treatment and survival of patients with cervical cancer admitted to Maputo Central Hospital (MCH) in 2016 to 2018. Sociodemographic, clinical and cancer-related data were retrieved from clinical records of patients admitted to the Oncology Service of the MCH with an incident cervical cancer in 2016 to 2018 (n = 407). The Pathology Service database was used to obtain information regarding pathological diagnosis. Survival data was obtained through the MCH Cancer Registry and clinical records. Odds ratios for the association between patients' characteristics and the diagnosis of advanced stage cancer were computed using logistic regression. Survival analyses were performed using the Kaplan-Meier estimator. A total of 91.2% of the patients were diagnosed with advanced disease (stage IIB-IV) and squamous cell carcinoma was the predominant histological subtype. Most of the patients underwent chemotherapy (93.1%) but <7% were submitted to surgery, radiotherapy or brachytherapy. Those living with HIV had 3.4-fold higher odds of advanced disease. Overall survival was 72.7% (95% confidence interval [CI]: 67.9-77.0) at 1-year and 51.0% (95%CI: 45.3-56.3) at 2-years. Those with early stage (IA-IIA) and asymptomatic at diagnosis had a significantly higher 2-year overall survival. In Mozambique, cervical cancer is diagnosed mostly in advanced stages, resulting in poor prognosis. This highlights the importance of HPV vaccination and screening, to decrease the burden of cervical cancer in this context.

Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

PURPOSE: We aimed to assess the impact of surgery of primary tumor in overall survival (OS) of women with de novo metastatic breast cancer. METHODS: Nationwide, population-based retrospective cohort study of women diagnosed with de novo metastatic breast cancer in Belgium, between Jan/2010-Dec/2014. Data was obtained from the Belgian Cancer Registry and administrative databases. "Surgery" group was defined by surgery of primary tumor up to nine months after diagnosis. We excluded women who did not receive systemic treatment or did not complete nine months follow-up after diagnosis. All the subsequent analyses reporting on overall survival and the stratified outcome analyses were performed based on this nine-month landmark cohort. OS was estimated using Kaplan-Meier method and compared using adjusted Cox proportional hazards models controlling for confounders with 95% confidence intervals (CI). We performed a stratified analysis according to surgery timing and a propensity score matching analysis. RESULTS: 1985 patients, 534 (26.9%) in the "Surgery" and 1451 (73.1%) in the "No Surgery" group. Patients undergoing surgery were younger (p < 0.001), had better performance status (PS) (p < 0.001), and higher proportion of HER2-positive and triple-negative breast cancer (p = 0.012). Median follow-up was 86.0 months (82.6-88.5). Median OS was 60.1 months (57.1-68.2) in the "Surgery" vs. 41.9 months (39.8-44.2) in the "No Surgery" group (adjusted HR 0.56; 0.49-0.64). OS was similar when surgery was performed upfront or after systemic treatment. Propensity score matching analysis confirmed the same findings. CONCLUSION: Among patients receiving systemic treatment for de novo metastatic breast cancer and surviving nine months or more, those who received surgery of the primary tumor within nine months of diagnosis have longer subsequent survival than those who did not.

Prevalence and associated factors of diabetic retinopathy in Latin American countries: a scoping review / Prevalência e fatores associados à retinopatia diabética em países da América Latina: uma revisão de escopo

ABSTRACT Objective To gather the available evidence in the literature on the prevalence and associated factors of diabetic retinopathy (DR) in Latin America. Methods This scoping review was developed according to the PRISMA-ScR. Prevalence data were summarized by weighted mean, considering the type of DM and country. For the analysis of associated factors, meta-analyses were performed with the most homogeneous studies, and the ORs and their 95%CIs were calculated. Results Forty-two articles published between 2004 and 2020 were included in this study. The mean prevalence of DR ranged from 15.0% in Costa Rica to 32.7% in Brazil. Conclusion This variation may be related to the diagnostic method, age of the studied population, duration of disease, glycemic control, or other associated factors such as the presence of diabetic nephropathy or hypertension. This review discloses an important burden of DR in Latin America and highlights the need for further in-country studies.

RESUMO Objetivo O objetivo desta revisão foi reunir as evidências disponíveis na literatura sobre a prevalência e os fatores associados à retinopatia diabética na América Latina. Métodos Esta é uma revisão de escopo desenvolvida de acordo com o PRISMA-ScR. Os dados de prevalência foram resumidos por média ponderada, considerando o tipo de diabetes mellitus e o país. Para a análise dos fatores associados, foram realizadas metanálises com os estudos mais homogêneos e calculados as razões de chance e seus intervalos de confiança de 95%. Resultados Foram publicados 42 artigos entre 2004 e 2020, os quais foram incluídos neste estudo. A prevalência média de retinopatia diabética variou de 15,0%, na Costa Rica, a 32,7%, no Brasil. Conclusão Essa variação pode estar relacionada ao método de diagnóstico, à idade da população estudada, à duração da doença, ao controle glicêmico ou a outros fatores associados, como a presença de nefropatia diabética ou hipertensão. Esta revisão revelou um ônus importante da retinopatia diabética na América Latina e destaca a necessidade de mais estudos nos países.

Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review.

BACKGROUND: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy. MATERIALS AND METHODS: The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases. RESULTS: 2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study. CONCLUSIONS: Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.

Value of cardiac magnetic resonance on the risk stratification of cardiomyopathies.

Cardiomyopathies represent a diverse group of heart muscle diseases with varying etiologies, presenting a diagnostic challenge due to their heterogeneous manifestations. Regular evaluation using cardiac imaging techniques is imperative as symptoms can evolve over time. These imaging approaches are pivotal for accurate diagnosis, treatment planning, and optimizing prognostic outcomes. Among these, cardiovascular magnetic resonance (CMR) stands out for its ability to provide precise anatomical and functional assessments. This manuscript explores the significant contributions of CMR in the diagnosis and management of patients with cardiomyopathies, with special attention to risk stratification. CMR's high spatial resolution and tissue characterization capabilities enable early detection and differentiation of various cardiomyopathy subtypes. Additionally, it offers valuable insights into myocardial fibrosis, tissue viability, and left ventricular function, crucial parameters for risk stratification and predicting adverse cardiac events. By integrating CMR into clinical practice, clinicians can tailor patient-specific treatment plans, implement timely interventions, and optimize long-term prognosis. The non-invasive nature of CMR reduces the need for invasive procedures, minimizing patient discomfort. This review highlights the vital role of CMR in monitoring disease progression, guiding treatment decisions, and identifying potential complications in patients with cardiomyopathies. The utilization of CMR has significantly advanced our understanding and management of these complex cardiac conditions, leading to improved patient outcomes and a more personalized approach to care.

Impact of disease duration on proteomic bioprofile and prognosis in rheumatoid arthritis patients.

OBJECTIVES: Cardiovascular disease worsens the prognosis of rheumatoid arthritis (RA) and vice-versa. Inflammation may be a common pathway for both conditions. It is expected that a longer RA duration leads to a greater inflammatory cumulative exposure burden; however, studies on the association between RA disease duration and outcomes are scarce. Our aim is to compare the characteristics, biomarker expression and outcomes according to the duration of RA. METHODS: Prospective cohort study including 399 RA patients, with detailed clinical, echocardiographic, and proteomic phenotyping that were compared across tertiles of RA disease duration. Cox proportional models were used to study the association of disease duration with cardiovascular outcomes. RESULTS: RA duration tertiles were: tertile 1 with median of 3.2; tertile 2 with median of 8.8; and tertile 3 with median of 21.8 years. Compared to tertile 1, patients in tertile 3 were older, had more erosive disease, more frequent echocardiographic alterations, lower haemoglobin and walked a shorter distance on the 6MWT. Natriuretic peptides, cathepsin L1, galectin 9, matrix metalloproteinase-12, adrenomedullin and tumour necrosis factor receptor 11A were higher in patients with longer disease duration. Compared to patients in tertile 1, those in tertile 3 had higher risk of a subsequent cardiovascular hospitalisation or cardiovascular death (HR 2.71, 95%CI 1.06-6.92, p=0.04). CONCLUSIONS: RA patients with longer disease duration had more organ damage and worse outcomes than those with shorter disease duration. Biomarker expression suggested that patients with longer RA duration had activation of pathways related to inflammation, extracellular matrix organisation, fibrosis and congestion.

Myocardial deformation analysis using cardiac magnetic resonance in apical hypertrophic cardiomyopathy: is it an useful tool to predict adverse outcomes?

Apical hypertrophic cardiomyopathy (AHCM) has a broad phenotypic spectrum and still poses many diagnostic and prognostic challenges. Our team performed a retrospective study to examine the prognostic value of myocardial deformation obtained with cardiac magnetic resonance tissue tracking (CMR-TT) analysis in predicting adverse events in AHCM patients. We included patients with AHCM referred to CMR in our department from August 2009 to October 2021. CMR-TT analysis was performed to characterize the myocardial deformation pattern. Clinical, other complementary diagnostic exams characteristics and follow-up data were analysed. Primary endpoint was the composite of all-cause hospitalizations and mortality. During the 12-year period, 51 AHCM patients were evaluated by CMR, with a median age of 64 years-old and male predominance. 56,9% had an echocardiogram suggestive of AHCM. The most frequent phenotype was "the relative form" (43,1%). CMR evaluation revealed a median maximum left ventricle thickness of 15 mm and the presence of late gadolinium enhancement in 78,4%. Applying CMR-TT analysis, median global longitudinal strain was - 14,4%, with a median global radial strain of 30,4% and global circumferential strain of -18,0%. During a median follow-up of 5,3 years, the primary endpoint occurred in 21,3% of patients, with a hospitalization rate of 17,8% and all-cause mortality rate of 6,4%. After multivariable analysis, longitudinal strain rate in apical segments was an independent predictor of the primary endpoint (p = 0,023), showing that CMR-TT analysis could be useful in predicting adverse events in AHCM patients.

Evaluation of Antibiotic Prophylaxis Prescriptions for Infectious Endocarditis Before Oral Procedures Between Cardiologists and Dentists

Abstract Background Infective endocarditis (IE) is a serious disease with a high mortality rate. Antibiotic prophylaxis for bacterial endocarditis before invasive procedures has been recommended in patients with predisposing cardiac conditions since 1960, but contemporary guidelines worldwide have proposed changes. Objective To evaluate the knowledge and pattern of prescription by cardiologists and dentists regarding antibiotic prophylaxis for bacterial endocarditis before risky oral procedures. Methods This is an observational and cross-sectional study. Data were obtained from an online questionnaire, sent to cardiologists and dentists linked to specialty societies, in the first semester of 2021. Data analysis was performed using descriptive statistics, and comparisons between variables were done in an exploratory approach. The significance level adopted was 5%. Results From 613 responders, 82.5% of cardiologists and 79.5% of dentists reported prescribing antibiotic prophylaxis for patients at high and moderate risk for IE. Of dental procedures capable of generating bacteremia, all were correctly identified by more than 50.0% of the sample. As for the habits of daily living, flossing and toothbrushing had almost 50.0% of correct answers, chewing had only 17.3%, and 40.9% reported that none of the actions presented a risk of bacteremia. When comparing variables, the correct prescription of amoxicillin (2 g, 30-60 minutes before the procedure) was more prevalent among cardiologists and in responders with less than 20 years of graduation (p<0.01). Conclusion In the present study, the prescription of antibiotic prophylaxis for IE were frequent for high- and moderate-risk patients, before oral/dental procedures. Partial knowledge was found about endocarditis, which highlights the need for continuous medical/dental education.

Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren's syndrome: evidence- and practice-based guidance.

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.

Biologic therapy in large and small vessels vasculitis, and Behçet's disease: Evidence- and practice-based guidance.

OBJECTIVE: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD). METHODS: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved. RESULTS: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations. CONCLUSION: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions.

Systemic treatment for neuroendocrine non-small cell lung carcinoma: A cases series and a systematic review of the literature.

INTRODUCTION: Neuroendocrine lung cancer constitutes a continuum from carcinoid tumours (CT) to large cell neuroendocrine (LCNEC) and small-cell carcinomas (SCLC). Except for SCLC, there is no consensual agreement on systemic therapy. The aim of this study is to review our clinical experience among patients with CT and LCNEC in the light of a systematic review of the literature. METHODS: A retrospective study of all patients with CT and LCNEC receiving a systemic therapy at Institut Jules Bordet and Erasme Hospital between 01/01/2000-31/12/2020. A systematic review of the literature was performed in Ovid Medline. RESULTS: 53 patients (21 CT and 32 LCNEC) were included. Despite limited response rates, patients with CT receiving a "carcinoid-like" 1st-line regimen (somatostatin analogues (SSA), everolimus, peptide receptor radionuclide therapy (PRRT)) had a numerically longer survival compared to those receiving other type of regimens (median 51.4 vs 18.6 months, respectively; p = 0.17). We observed a similar survival between 1st line "SCLC-like" vs "non-small cell lung cancer (NSCLC)-like" schemes in LCNEC (median 11.2 vs 12.6 months, respectively; p = 0.46). The systematic review identified 23 studies (12 prospective, 15 and 8 for CT and LCNEC respectively). For CT, everolimus and SSA led to prolonged disease control with an acceptable toxicity profile, while higher response rates but lower tolerance were associated with PRRT and chemotherapy regimens including oxaliplatine and dacarbazine. For LCNEC, no difference emerged when comparing "SCLC-like" and "NSCLC-like" regimens considering response rate, progression-free or overall survival. CONCLUSIONS: SSA, everolimus and PRRT present a good therapeutic index for CT, while the role of chemotherapy remains limited to aggressive and rapidly evolving CT. The best type of chemotherapy regimen remains an open question in LCNEC.