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Introduction The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic.Areas covered Here, the authors discuss the history of hydroxychloroquine and chloroquine, the in vitro data which led to their widespread repurposing and adoption in COVID-19 and their complex pharmacokinetics. The evidence for the use of these drugs is assessed through in vivo animal experiments and the wealth of conflicting data and interpretations published during COVID-19, including the more informative results from randomized controlled trials (RCTs). The safety aspects of these drugs, in particular cardiotoxicity, are then reviewed.Expert opinion The evidence from clinical trials in COVID-19 supports the well-established safety record of the 4-aminoquinolines at currently recommended dosage. In hospitalized patients with severe COVID-19 RCTs show clearly that the 4-aminoquinolines are not beneficial. The only treatments with proven benefit at this stage of infection are immunomodulators (dexamethasone, IL-6 receptor antagonists). No antiviral drugs have proven life-saving in late-stage COVID-19.

Poly (ADP-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings of epithelial ovarian cancers (EOCs) with BRCA 1-2 gene mutation. PARP inhibitors are the first example of drugs targeting the loss of a gene suppressor they block base-excision repair in the cancer cells, which have lost homologous recombination due to BRCA-mutation, resulting in loss of DNA repair and cell death, also known as synthetic lethality.

This article provides an overview of PARP inhibitors in OC treatment and also an extensive section on the combined strategies of PARP inhibitors, including approved as well as currently investigated drugs. STAT inhibitor It also offers a section on the use of predictive biomarkers for PARP inhibitors treatment. Ongoing trials, including novel combinations, are discussed.

In recent years, there is increasing evidence that PARP inhibitor therapy can have life-long percussion in the treatment of EOC, even if some questions have to be solved yet, such as its use in combination therapy, the possibility to retreat with a PARP inhibitor, and finally how to overcome a resistance mechanism to this therapy. In this way, PARP inhibitors can obtain an important role in making a personalized therapeutic program in the case of first-line, neoadjuvant, platinum-sensitive, and resistant high-grade serous OC treatment.

In recent years, there is increasing evidence that PARP inhibitor therapy can have life-long percussion in the treatment of EOC, even if some questions have to be solved yet, such as its use in combination therapy, the possibility to retreat with a PARP inhibitor, and finally how to overcome a resistance mechanism to this therapy. In this way, PARP inhibitors can obtain an important role in making a personalized therapeutic program in the case of first-line, neoadjuvant, platinum-sensitive, and resistant high-grade serous OC treatment.

In the present prospective multicentre observational study, we evaluated the potential role of blood eosinophils on the outcomes of patients hospitalized for COPD exacerbations.

Consecutive patients >40years with a previous COPD diagnosis were recruited. Blood eosinophils were measured on admission prior to the initiation of treatment and were evaluated in three groups (<50, 50-149 and ≥150 cells/μL). Patients received standard care and were followed up for a year.

A total of 388 patients were included (83.5% male, mean age 72years). Patients with higher blood eosinophils had less dyspnoea (Borg scale), lower C-reactive protein (CRP) and higher PaO

/FiO

(partial pressure for oxygen/fraction of inhaled oxygen), and were discharged earlier (median 11 vs. 9 vs. 5days for patients with <50, 50-149 and ≥150 cells/μL, respectively). Patients with <50 cells/μL presented higher 30-day and 1-year mortality, whereas there were no differences in moderate/severe COPD exacerbations between the three groups. In a post hoc analysis, treatment with inhaled corticosteroids as per physicians' decision was associated with better exacerbation prevention during follow-up in patients with ≥150 cells/μL.

Higher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker.

Higher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker.Introduction Despite advances in imaging technology to guide ablative therapies, catheter ablation of more complex arrhythmias continues to be a challenge in part due to suboptimal mechanistic understanding of these arrhythmias by conventional mapping systems. A novel noncontact charge density mapping system has been designed to overcome some of these limitations.Areas covered Hereby, we present an overview of this novel, charge density-based global chamber mapping approach. We initially highlight the concept of charge density, describe further the device technology and finally summarize the clinical application of this system.Expert opinion Noncontact charge density mapping provides a more localized, high-resolution global panoramic assessment of cardiac activation. This might contribute to uncover the mechanisms of more complex arrhythmias such as persistent atrial fibrillation or unstable atrial tachycardias with the ultimate goal to guide the ablation therapy.

Although international clinical practice guidelines recognize a continued role for menopausal hormone therapy (HT), particularly for symptomatic women <60 years of age or within 10 years of menopause, safety and tolerability concerns have discouraged HT use due to potential links with a perceived increased risk of hormone-dependent cancers, and an established risk of stroke and venous thromboembolism. There is therefore a need for safe, effective non-hormonal therapy for relief of vasomotor symptoms (VMS) associated with menopause.

This narrative review summarizes the dataset accrued for fezolinetant, a neurokinin-3 receptor (NK3R) antagonist in clinical development for menopause-associated VMS.

Altered signaling in neuroendocrine circuits at menopause leads to VMS wherein NK3R activity plays a key role to modulate the thermoregulatory center in a manner conducive to triggering the 'hot flash' response. Thus, a new generation of NK3R antagonists has entered clinical development to specifically target the mechanistic basis of VMS.