Background
Identification of reliable outcome predictors in coronavirus disease 2019 (COVID‐19) is of paramount importance for improving patient's management.
Methods
A systematic review of ...literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in‐hospital mortality. We extracted numeric data on patients’ characteristics and cases with adverse outcomes and employed inverse variance random‐effects models to derive pooled estimates.
Results
We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26‐4.41), acute cardiac (OR = 10.58, 5.00‐22.40) or kidney (OR = 5.13, 1.78‐14.83) injury, increased procalcitonin (OR = 4.8, 2.034‐11.31) or D‐dimer (OR = 3.7, 1.74‐7.89), and thrombocytopenia (OR = 6.23, 1.031‐37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D‐dimer conferred an increased risk of in‐hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934‐6.73), but not with mortality.
Conclusions
Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in‐hospital mortality.
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Advanced-inoperable cervical cancer is a challenging entity due to increased percentage of locoregional and distant recurrences. Furthermore, recurrent cervical cancer not amenable to ...radical treatment as well as de novo metastatic disease are considered incurable with dismal prognosis. Well-designed clinical trials conducted during the last 30 years have revealed the active chemotherapeutic agents as well as their optimal combinations. The rational approach that has led to the current treatment algorithms as well as the introduction of targeted therapies based on the knowledge of the molecular pathogenesis of the disease are discussed in this review.
Since 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), impaired public health with considerable morbidity and mortality due to the lack of vaccines and effective treatment. The ...severe disease mainly harmed adults with predisposing medical comorbidities (such as heart disease, hypertension, chronic lung disease), while it can occur in healthy individuals that may be asymptomatic. Wastewater-based Epidemiology (WBE), a non-invasive, objective, chemical tool was used to monitor and estimate the changes in drug's consumption and prescription patterns under normal conditions (2019) and under COVID-19 pandemic conditions (2020). NSAIDs, antihypertensives, diuretics, antiepileptics, antilipidemics, antibiotics, analgesics, antivirals, anticancer drugs, contrast iodinated drugs, antidiabetics, antiallergic drugs, antiulcers and other pharmaceuticals were studied in wastewater and revealed the application of various treatments during the first wave of the pandemic in Athens, Greece. Data were correlated with COVID-19 infection therapeutical plans. The result of the analysis revealed a remarkable increase for antiviral drugs (170%), hydroxychloroquine (387%), and antibiotics (57%), which were the most applied treatments against COVID-19 during the first wave in Greece. In agreement with related authorities urge, NSAIDs presented decrease (27%) during the first lockdown, while paracetamol demonstrated a remarkable increase (198%). The use levels for Angiotensin II receptor blockers such as valsartan, and co-administrated diuretics, such as hydrochlorothiazide, were reduced during 2020, by 32% and 26% respectively.
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•Significant increase was observed for antiviral drugs (170%) and paracetamol (198%).•Hydroxychloroquine consumption showed a 387% increase during lockdown.•The consumption levels for hypertensive agents were reduced in 2020.•Antibiotics demonstrated a noteworthy increase (57%).•NSAIDs consumption showed a 27% decrease during lockdown.
Aims
SARS‐CoV‐2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers 4 months after ...COVID‐19 infection.
Methods and results
In a case‐control prospective study, we included 70 patients 4 months after COVID‐19 infection, 70 age‐ and sex‐matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow‐mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV), (v) global left and right ventricular longitudinal strain (GLS), and (vi) malondialdehyde (MDA), an oxidative stress marker, thrombomodulin and von Willebrand factor as endothelial biomarkers. COVID‐19 patients had similar CFR and FMD as hypertensives (2.48 ± 0.41 vs. 2.58 ± 0.88, P = 0.562, and 5.86 ± 2.82% vs. 5.80 ± 2.07%, P = 0.872, respectively) but lower values than controls (3.42 ± 0.65, P = 0.0135, and 9.06 ± 2.11%, P = 0.002, respectively). Compared to controls, both COVID‐19 and hypertensives had greater PBR5–25 (2.07 ± 0.15 µm and 2.07 ± 0.26 µm, P = 0.8 vs. 1.89 ± 0.17 µm, P = 0.001), higher PWV (carotid–femoral PWV 12.09 ± 2.50 vs. 11.92 ± 2.94, P = 0.7 vs. 10.04 ± 1.80 m/s, P = 0.036) and impaired left and right ventricular GLS (−19.50 ± 2.56% vs. −19.23 ± 2.67%, P = 0.864 vs. −21.98 ± 1.51%, P = 0.020 and −16.99 ± 3.17% vs. −18.63 ± 3.20%, P = 0.002 vs. −20.51 ± 2.28%, P < 0.001). MDA and thrombomodulin were higher in COVID‐19 patients than both hypertensives and controls (10.67 ± 0.32 vs 1.76 ± 0.03, P = 0.003 vs. 1.01 ± 0.05 nmol/L, P = 0.001 and 3716.63 ± 188.36 vs. 3114.46 ± 179.18 pg/mL, P = 0.017 vs. 2590.02 ± 156.51 pg/mL, P < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers.
Conclusions
SARS‐CoV‐2 may cause endothelial and vascular dysfunction linked to impaired cardiac performance 4 months after infection.
The landscape of local and systemic therapy of renal cell carcinoma (RCC) is rapidly changing. The increase in the incidental finding of small renal tumors has increased the application of ...nephron‐sparing procedures, while ten novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin pathways, or inhibiting the interaction of the programmed death 1 receptor with its ligand, have been approved since 2006 and have dramatically improved the prognosis of metastatic RCC (mRCC). These rapid developments have resulted in continuous changes in the respective Clinical Practice Guidelines/Expert Recommendations. We conducted a systematic review of the existing guidelines in MEDLINE according to the Preferred Reporting Items for Systematic Review and Meta‐Analyses statement, aiming to identify areas of agreement and discrepancy among them and to evaluate the underlying reasons for such discrepancies. Data synthesis identified selection criteria for nonsurgical approaches in renal masses; the role of modern laparoscopic techniques in the context of partial nephrectomy; selection criteria for cytoreductive nephrectomy and metastasectomy in mRCC; systemic therapy of metastatic non‐clear‐cell renal cancers; and optimal sequence of available agents in mRCC relapsed after anti‐VEGF therapy as the major areas of uncertainty. Agreement or uncertainty was not always correlated with the availability of data from phase III randomized controlled trials. Our review suggests that the combination of systematic review and critical evaluation can define practices of wide applicability and areas for future research by identifying areas of agreement and uncertainty among existing guidelines.
Implications for Practice
Currently, there is uncertainity on the role of surgery in MRCC and on the choice of available guidelines in relapsed RCC. The best practice is individualization of targeted therapies. Systematic review of guidelines can help to identify unmet medical needs and areas of future research.
Therapy options for renal cell carcinoma are developing rapidly. This systematic review focuses on the current guidelines for treatment of renal cell carcinoma.
Overweight, obesity, and metabolic syndrome (MetS) have become epidemic conditions affecting 39%, 13%, and 20% of the population respectively. The aim of this article is to review the literature on ...the association of obesity and MetS with the risk of cancer. We also explore the effect of lifestyle modifications, such as diet, physical activity, and antidiabetic medications, on cancer incidence. Increased body mass index (BMI) has been associated with a multitude of site-specific cancers, reaching relative risk (RR) 1.54 95% confidence interval (CI) 1.47–1.61 per 5 unit increase for endometrial cancer, as well as with overall cancer risk (RR 1.03, 95% CI 1.02–1.05). Central adiposity measured by waist circumference or waist-to-hip ratio has been suggested as a stronger predictor than BMI for several cancers, such as colorectal cancer. Metabolic Syndrome has been consistently and positively associated with the risk of very common cancers like colorectal (RR 1.34, 95% CI 1.24–1.44), endometrial (RR 1.62, 95% CI 1.26–2.07) and postmenopausal breast cancer (RR 2.01, 95% CI 1.55–2.60). Hyperglycemia and subsequently T2DM have been also shown to increase the risk of cancer. Nevertheless, these risk factors are modifiable and therefore implementing lifestyle modifications could prevent an important number of cancer cases. Adherence to cancer prevention guidelines, including maintaining a healthy weight, having regular physical exercise (RR 0.58–0.90 for different cite specific cancers) and following a healthy dietary pattern (RR 0.74–0.94 for different cite specific cancers) have a protective effect on the risk of cancer. The strength of this review is the presentation of the best evidence, as the data derive mainly from meta-analyses. Public health policies should focus on the modification of risk factors and future research is needed to reveal the pathophysiological links between these risk factors and cancer to develop more efficient prevention and treatment strategies.
COVID-19 pandemic spread rapidly worldwide with unanticipated effects on mental health, lifestyle, stability of economies and societies. Although many research groups have already reported SARS-CoV-2 ...surveillance in untreated wastewater, only few studies evaluated the implications of the pandemic on the use of chemicals by influent wastewater analysis. Wide-scope target and suspect screening were used to monitor the effects of the pandemic on the Greek population through wastewater-based epidemiology. Composite 24 h influent wastewater samples were collected from the wastewater treatment plant of Athens during the first lockdown and analyzed by liquid chromatography mass spectrometry. A wide range of compounds was investigated (11,286), including antipsychotic drugs, illicit drugs, tobacco compounds, food additives, pesticides, biocides, surfactants and industrial chemicals. Mass loads of chemical markers were estimated and compared with the data obtained under non-COVID-19 conditions (campaign 2019). The findings revealed increases in surfactants (+196%), biocides (+152%), cationic quaternary ammonium surfactants (used as surfactants and biocides) (+331%), whereas the most important decreases were estimated for tobacco (−33%) and industrial chemicals (−52%). The introduction of social-restriction measures by the government affected all aspects of life.
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•Findings reflect the effects of pandemic and social distancing.•Wastewater-based epidemiology was used to assess the exposure to various chemicals.•Significant changes in illicit drug consumption were observed.•Surfactants and biocides showed a notable increase 196% and 152%, respectively.•Significant reduction of the industrial chemicals (52%) due to business closure
Summary
Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and lower seroconversion ...rates following coronavirus disease 2019 (COVID‐19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS‐CoV‐2 in non‐vaccinated patients with MM and COVID‐19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration‐approved enzyme‐linked immunosorbent assay methodology. Thirty‐five patients with COVID‐19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID‐19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6–94%) and 58·7% (21·4–91·8%) for COVID‐19‐positive and vaccinated patients, respectively (P = 0·01).Importantly, there was no difference in NAb production between COVID‐19‐positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID‐19 should be considered for booster vaccine doses.
Despite the increasing number of treatment options available for multiple myeloma, relapse is still inevitable and there remains a critical unmet need for treatments for patients with late-stage, ...highly refractory disease. In this review, we discuss currently approved treatment options for heavily pretreated patients with relapsed and refractory multiple myeloma, with a focus on the optimal management of patients with MM refractory to lenalidomide, bortezomib, and in some cases, daratumumab or an anti-CD38 monoclonal antibody. Data from recent clinical trials of immunomodulatory agents (pomalidomide), proteasome inhibitors (PIs; carfilzomib and ixazomib), monoclonal antibodies (elotuzumab, daratumumab, and isatuximab), and other novel therapies (including panobinostat-based therapy) are summarized. We also provide potential therapeutic strategies for patients according to different treatment histories, and include case studies to illustrate the practical use of various treatment options in a clinical setting. Regimens containing pomalidomide, elotuzumab, next-generation PIs, panobinostat, or selinexor may provide effective treatment options in patients with triple-refractory disease. The choice of agents used, and combinations thereof should be individualized as well as strategically planned from early- to late-stage relapse.
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