COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. ...Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients. Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.
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.
Waldenström macroglobulinemia (WM) is an uncommon lymphoma characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M (IgM). The ...disease may have an asymptomatic phase, or patients may present with symptoms and complications resulting from marrow or other tissue infiltration, or from physicochemical or immunological properties of the monoclonal IgM. Diagnosis of WM has been clearly defined, and genetic testing for somatic mutation of MYD88L265P is a useful tool for differential diagnosis from other conditions. Specific criteria that define symptomatic disease that needs treatment offer clinical guidance. The treatment of WM has evolved rapidly, with treatment options that include anti-CD20 monoclonal antibody-based combinations and BTK inhibitors. The choice of therapy is based on the need for rapid disease control, presence of specific disease complications, and patient's age. With the use of BTK inhibitors, the use of continuous therapy has been introduced as another option over fixed-duration chemoimmunotherapy. In this review, we focus on different clinical scenarios and discuss treatment options, based on the available data.
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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.
Bone disease is a cardinal complication of multiple myeloma that affects quality of life and survival. Osteocytes have emerged as key players in the development of myeloma-related bone disease. Along ...with other factors, they participate in increased osteoclast activity, decreased osteoblast function, and immunosuppressed marrow microenvironment, which deregulate bone turnover and result in bone loss and skeletal-related events. Denosumab is a novel alternative to bisphosphonates against myeloma bone disease. Special considerations in this constantly evolving field are thoroughly discussed.
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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.
How I treat relapsed multiple myeloma Kastritis, Efstathios; Terpos, Evangelos; Dimopoulos, Meletios A.
Blood,
05/2022, Letnik:
139, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Despite recent advances, multiple myeloma remains an incurable disease for most patients, and initial remission will be followed by relapses requiring therapy. For many, there will be several ...remissions and relapses until resistance develops to all available therapies. With the introduction of several new agents, myeloma treatment has changed drastically, and there are new options for the management of relapsed or refractory disease, including new drug classes with distinct mechanisms of action and cellular therapies. However, resistance to major drug classes used in first-line remains the most critical factor for the choice of treatment at relapse. Continuous lenalidomide-based therapy is used extensively at first-line, and resistance to lenalidomide has become the key factor for the choice of salvage therapy. Daratumumab is increasingly used in first-line, and soon patients that relapse while on daratumumab will become a common challenge. Three-drug regimens are the standard approach to manage relapsed disease. Adding drugs with new mechanisms of activity can improve outcomes and overcomes class resistance, but, until now, while biology is important, it can offer only limited guidance for the choice of therapy.
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Summary
Immunoglobulin light chain (AL) amyloidosis, the most common of the systemic amyloidosis, is characterized by the deposition of amyloid fibrils that derive from the aggregation of misfolded ...monoclonal immunoglobulin light chains. Amyloid fibrils disrupt tissue architecture and the pre‐fibril oligomers are directly toxic to myocardiac cells, causing cardiac dysfunction. The lethal consequences of AL amyloidosis are due to the toxic product and not due to the malignant behaviour of the plasma cell clone; however, the characteristics of this clone are associated with long‐term prognosis. Early and accurate diagnosis is the key to effective management, but is challenging. Modern chemotherapy options (including autologous transplantation, bortezomib, lenalidomide) have improved the outcomes of patients at low or intermediate risk, but the prognosis of patients with severe cardiac dysfunction is still poor. Therapies targeting amyloid deposits and the amyloidogenic process are under investigation and offer promise for better future treatments.
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.
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