Safety of lorlatinib in ALK-positive non-small-cell lung cancer and management of central nervous system adverse events.

The use of tyrosine kinase inhibitors has made a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Recently, lorlatinib, a third-generation tyrosine kinase inhibitor, has demonstrated significant systemic and intracranial activity in both first-line and subsequent-line therapy in ALK-positive NSCLC patients. In this review, general characteristics of lorlatinib, its efficacy in the treatment of ALK-positive NSCLC patients and the safety of lorlatinib, particularly addressing central nervous system adverse events, are discussed. Management of central nervous system adverse events, which seem to be specific to lorlatinib therapy, is outlined.

Lung cancer is a common disease and affects patients badly. Lorlatinib is a new and useful drug for this disease. But this drug has also some undesirable effects for the brain. These effects are generally mild and can be treated. This article discusses the undesirable effects of this drug on the brain and how to cope with these effects.

Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series.

INTRODUCTION: Clozapine-induced myocarditis or any clozapine-induced inflammation may be a hypersensitivity reaction due to titration that was too rapid for the patient's clozapine metabolism. Clozapine metabolism is influenced by ancestry, sex, smoking and the presence of confounders including obesity, infections, and inhibitors (e.g., valproate) causing the patient to behave as a clozapine poor metabolizer (PM). A published study in a Turkish hospital identified 1 case of clozapine-induced pancreatitis and hepatitis and 9 cases of clozapine-induced myocarditis. To explore the hypothesis that the 10 patients were clozapine PMs, their serum clozapine concentrations were investigated using concentration-to-dose (C/D) ratios and their titrations carefully reviewed. METHODS: Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed. RESULTS: All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83mg/day). Nine of the 10 patients may have behaved as clozapine PMs due to obesity and/or valproate co-prescription during titration. One also had an undiagnosed infection. Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high. CONCLUSIONS: Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced inflammation could be explained by lack of individualized titration.

Do Changes in Body Shape Due to Pregnancy Lead to Cosmetic Surgery? A Cross-Sectional Study.

OBJECTIVE: Pregnants and puerperas show different perceptions of their body image and appearance, so authors investigated their perceptions related to pregnancy and puerperium, evaluating their views on cosmetic surgery, by a cross-sectional study. MATERIALS AND METHODS: 5-item questionnaires were administrated to women at first pregnancy and puerperas. Patients were submitted also to Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Body Image Inventory (BII) analysis, indicating the level of anxiety, depression and body dissatisfaction for somatic changes during pregnancy and after childbirth. RESULTS: 186 healthy women, aged between 25-35 years, equally divided in pregnancy and puerperium, were compared in terms of body image, with no significant difference between groups. Analyzing the item "cosmetic surgery is required after all pregnancies", there was a significant difference in puerperas and the item "cosmetic surgery is necessary for postpartum" was the principal. The comparison of BII, BDI, BAI values between pregnants and puerperas showed a significant difference between groups (p<0.00), with higher scores in postpartum patients. CONCLUSION: Body shape and physical dissatisfaction during pregnancy is linked with increased risk of depression in pregnancy and puerperium, pushing women to opt for cosmetic surgery, especially in puerperium.

Perspectives, fears and expectations of patients with gynaecological cancers during the COVID-19 pandemic: A Pan-European study of the European Network of Gynaecological Cancer Advocacy Groups (ENGAGe).

BACKGROUND: The impact of the COVID-19 pandemic on European gynaecological cancer patients under active treatment or follow-up has not been documented. We sought to capture the patient perceptions of the COVID-19 implications and the worldwide imposed treatment modifications. METHODS: A patient survey was conducted in 16 European countries, using a new COVID-19-related questionnaire, developed by ENGAGe and the Hospital Anxiety & Depression Scale questionnaire (HADS). The survey was promoted by national patient advocacy groups and charitable organisations. FINDINGS: We collected 1388 forms; 592 online and 796 hard-copy (May, 2020). We excluded 137 due to missing data. Median patients' age was 55 years (range: 18-89), 54.7% had ovarian cancer and 15.5% were preoperative. Even though 73.2% of patients named cancer as a risk factor for COVID-19, only 17.5% were more afraid of COVID-19 than their cancer condition, with advanced age (>70 years) as the only significant risk factor for that. Overall, 71% were concerned about cancer progression if their treatment/follow-up was cancelled/postponed. Most patients (64%) had their care continued as planned, but 72.3% (n = 892) said that they received no information around overall COVID-19 infection rates of patients and staff, testing or measures taken in their treating hospital. Mean HADS Anxiety and Depression Scores were 8.8 (range: 5.3-12) and 8.1 (range: 3.8-13.4), respectively. Multivariate analysis identified high HADS-depression scores, having experienced modifications of care due to the pandemic and concern about not being able to visit their doctor as independent predictors of patients' anxiety. INTERPRETATION: Gynaecological cancer patients expressed significant anxiety about progression of their disease due to modifications of care related to the COVID-19 pandemic and wished to pursue their treatment as planned despite the associated risks. Healthcare professionals should take this into consideration when making decisions that impact patients care in times of crisis and to develop initiatives to improve patients' communication and education.

Columellar Scar Perception in Open Rhinoplasty. Interplay of Scar Awareness, Body Cathexis and Patient Satisfaction.

INTRODUCTION: Open and closed approaches for rhinoplasty have individual advantages and disadvantages; however, the resultant columellar scar of the open approach is directly considered as a disadvantage. This study focuses on the columellar scar awareness and its implications on overall satisfaction of the patients after open rhinoplasty. PATIENTS AND METHODS: A total of 91 patients who have undergone open rhinoplasty were included in this study. A written questionnaire algorithm consisting of 4 sequential questions was applied. Except for the first question [Do you have any scar(s) caused by any trauma, operation or any other reason on your face?], every question was answered on a scale from 1 to 5. The respondents were given the 25-question "Modified Body Cathexis Scale (MBCS)"and their scars graded using the "Columellar Scar Assessment Scale" (CSAS). The data were statistically interpreted. RESULTS: Of the 91 open rhinoplasty patients, 12 of them responded with a "yes" to the first question reporting their columellar scars. There was no significant difference with regards to patient satisfaction regarding these patients (p > 0.05). However, those who reported the scar yielded a significantly lower MBCS scores. 9 patients declared that they exerted effort to conceal their scars. Those who concealed their scars and those who did not yielded a significant difference in patient satisfaction. The CSAS scores of those who reported the columellar scar were significantly higher than those who did not. CONCLUSION: Our study suggests that MBSC can be a valuable tool for determining the impact of outcomes from the patient's standpoint, and awareness of the columellar scar is not related to patient satisfaction but with bodily perception. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .