The prevalence of rheumatic diseases in central Greece: a population survey

<p>Abstract</p> <p>Background</p> <p>Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece.</p> <p>Methods</p> <p>In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases.</p> <p>Results</p> <p>The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sjögren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension.</p> <p>Conclusions</p> <p>Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.</p

Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors

Cyclin-dependent kinase (CDK) 4/6 inhibitors have emerged in the treatment of metastatic hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, most patients will eventually present disease progression, highlighting the inevitable resistance of cancer cells to CDK4/6 inhibition. Several studies have suggested that resistance mechanisms involve aberrations of the molecules that regulate the cell cycle, and the re-wiring of the cell to escape CDK4/6 dependence and turn to alternative pathways. Loss of retinoblastoma function, overexpression of CDK 6, upregulation of cyclin E, overexpression of CDK 7, and dysregulation of several signaling pathways, notably the PI3/AKT/mTOR pathway, have been implicated in the development of resistance to CDK4/6 inhibitors. Overlap with endocrine resistance mechanisms might be possible. Combinational therapeutic strategies should be explored in order to prevent resistance and optimize the management of patients after progression under CDK 4/6 inhibition. © 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature

Pulmonary blastoma: A comprehensive overview of a rare entity

Introduction: Pulmonary blastoma is a rare malignancy, accounting for less than 0.5% of primary lung tumors. It belongs to the group of pulmonary sarcomatoid carcinomas, and it is typically characterized by a biphasic pattern of an epithelial and a mes-enchymal component. Only a few hundred cases have been reported worldwide. The aim of this study is to review and critically assess the literature regarding pulmonary blastoma. Material and methods: A narrative literature review of PubMed database from the inception of the database up to January 2021, limited to the English language, was conducted, using combinations of the following keywords: “pulmonary blastoma”, “biphasic pulmonary blastoma”, “sarcomatoid carcinoma”. Results: Pulmonary blastoma is composed of an epithelial and a mesenchymal malignant component. Regarding pathogenesis, the origin of the biphasic cell population remains elusive. Characteristic immunohistochemical stains are supportive of diagno-sis. Clinically, the symptomatology is non-specific, while 40% of the cases are asymptomatic. It is diagnosed at a younger age compared to other types of lung cancer, and it is often non-metastatic at diagnosis allowing for surgical treatment. Data on management and survival are scarce and mainly come from isolated cases. Advances on targeted therapy may provide novel treatment options. Given the rarity of the cases, multicenter collaboration is needed in order to establish therapeutic guidelines. © 2021 PTChP

Cyclin-dependent kinase (CDK) inhibitors in solid tumors: a review of clinical trials

Cyclin-dependent kinases (CDKs) play a key regulating role in the cell cycle, which is almost universally altered in cancer, leading to sustained proliferation. Early pan-CDK inhibitors showed poor results in clinical trials for solid malignancies, as the lack of selectivity produced significant toxicity. The production of more selective inhibitors led to significant developments in cancer therapy, as CDK4/6 inhibitors in combination with endocrine therapy changed the landscape of the treatment of hormone-receptor positive (HR +) metastatic breast cancer. Recently, Trilaciclib demonstrated benefits regarding hematological toxicity compared to placebo when administered in combination with chemotherapy in small cell lung cancer. Newer agents, such as SY-5609, a selective CDK7 inhibitor, have also shown promising results in early clinical trials. In this paper, we review the data from clinical trials of CDK inhibitors in solid tumors, either as a monotherapy or in combination with other agents, with an emphasis on novel agents and potential new indications for this drug class

Assessment of Seroconversion after SARS-CoV-2 Vaccination in Patients with Lung Cancer

Background: SARS-CoV-2 mortality rates are significantly higher in patients with lung cancer compared with the general population. However, little is known on their immunization status after vaccination. Methods: To evaluate the humoral response (seroconversion) of patients with lung cancer following vaccination against SARS-COV-2 (Group A), we obtained antibodies against SARS-CoV-2 spike (S) protein both at baseline and at different time points after the first dose of SARS-CoV-2 vaccine (two to three weeks [T1], six weeks ± one week [T2], 12 weeks ± three weeks [T3], and 24 weeks ± three weeks [T4]). Antibodies were also acquired from a control cohort of non-lung cancer patients (Group B) as well as a third cohort containing healthy controls (Group C) at all time points and at T4, respectively, to make comparisons with Group A. Analysis of antibody response at different time points, association with clinicopathologic parameters, and comparisons with control groups were performed. Results: A total of 125 patients with lung cancer were included in the analysis (96 males [74.3%], median age of 68 years [46–91]. All study participants received two vaccine doses (BNT162b2, mRNA-1273, AZD1222). Analysis of anti-SARS-CoV-2 S antibody titers showed minimal response at T1 (0.4 [0.4–48.6] IU/mL). Antibody response peaked at T2 (527.0 [0.4–2500] IU/mL) and declined over T3 (323.0 [0.4–2500] IU/mL) and T4 (141.0 [0.4–2500] IU/mL). Active smokers had lower antibody titers at T2 (p = 0.04), T3 (p = 0.04), and T4 (p &lt; 0.0001) compared with former or never smokers. Peak antibody titers were not associated with any other clinicopathologic charac-teristic. No significant differences were observed compared with Group B. However, lung cancer patients exhibited significantly decreased antibody titers compared with Group C at T4 (p &lt; 0.0001). Conclusions: Lung cancer patients demonstrate sufficient antibody response six weeks after the first dose of vaccine against SARS-CoV-2 when vaccinated with two-dose regimens. Rapidly declining antibody titers six weeks after the first dose underline the need for a third dose three months later, in patients with lung cancer, and especially active smokers. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Beneficial effects of intermediate dosage of anticoagulation treatment on the prognosis of hospitalized COVID-19 patients: The ETHRA study

Background/Aim: To investigate the efficacy (prognosis, coagulation/inflammation biomarkers) and safety (bleeding events) of different anticoagulation dosages in COVID-19 inpatients. Patients and Methods: COVID-19 inpatients (Athens, Greece) were included. The &quot;Enhanced dose THRomboprophylaxis in Admissions (ETHRA)&quot; protocol was applied in certain Departments, suggesting the use of intermediate anticoagulation dosage. The primary endpoint was a composite of intubation/venous thromboembolism/death. Inflammation/coagulation parameters were assessed. Results: Among 127 admissions, 95 fulfilled the inclusion criteria. Twenty-one events (4 deaths, 17 intubations) were observed. Regression analysis demonstrated significant reduction of events with intermediate or therapeutic dosage [HR=0.16 (95%CI=0.05-0.52) p=0.002; HR=0.17 (0.04-0.71) p=0.015, respectively]. D-Dimer values were higher in those who met the composite endpoint. Intermediate dosage treatment was associated with decreased values of ferritin. Three patients (3%) had minor hemorrhagic complications. Conclusion: Anticoagulation treatment (particularly intermediate dosage) appears to have positive impact on COVID-19 inpatients&apos; prognosis by inhibiting both coagulation and inflammatory cascades. © 2021 International Institute of Anticancer Research. All rights reserved

A phase ii study on the use of convalescent plasma for the treatment of severe covid-19-a propensity score-matched control analysis

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004–0.36), p: 0.005], significantly better overall survival by Kaplan–Meir analysis (p &lt; 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64–348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209). © 2021 by the au-thors. Licensee MDPI, Basel, Switzerland

Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis

Background: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. Methods: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). Findings: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20–0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO2/FiO2. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17–0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12–0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37–1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59–3·10]). Interpretation: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. Funding: Sobi. © 2021 Elsevier Lt