Increased breadth and neutralization of antibodies against SARS-CoV-2 variants after infection and vaccination: A serosurveillance study in pediatric patients of Southern Switzerland.

Little information is available about the nature of the immune response in children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. The aim of this study is to define the seroprevalence and the features of the antibody response in children of Southern Switzerland during the different waves of Coronavirus Disease 2019 (COVID-19) pandemic. By analyzing 756 sera collected from children aged 0 to 16 years admitted to the Institute of Pediatrics of Southern Switzerland during the prepandemic period (before March 2020) and the first four pandemic waves (between March 2020 and June 2022), we investigated binding titers, cross-reactivity, and neutralizing properties of the serum antibodies against SARS-CoV-2 variants. Seroprevalence varied from 6% during the first wave to 14% and 17% during the second and third waves, respectively, peaking at 39% during the fourth wave. The 96 seropositive cases were mostly asymptomatic (42.7%) or showed mild (20.8%) to moderate (32.3%) symptoms. Moderate symptoms and close contact with COVID-19-positive individuals were associated with a higher infection risk (P < 0.001). The antibody response was mainly driven by IgG directed to the receptor-binding domain (RBD) of Wuhan-1 SARS-CoV-2 Spike (S). Children infected in the first three waves produced antibodies with up to 11-fold and 5.5-fold reduction in binding and neutralizing titers, respectively, against different SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, BA.2, and BA.5. Such reductions were less pronounced in children infected during the fourth wave, who showed the highest frequency and titers of neutralizing antibodies against the same variants. Compared to infection, vaccination with a Wuhan-1-based messenger RNA (mRNA) vaccine induced higher and heterogenous levels of antibodies cross-reacting to the different SARS-CoV-2 variants analyzed.   Conclusions: Despite the high burden of COVID-19 in Southern Switzerland, we observed an initial low seroprevalence of SARS-CoV-2 in children, which increased in the later waves. The antibody response was poor in the first three waves and improved in the fourth wave, when children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants. What is Known: • Children were marginally affected by the initial SARS-CoV-2 variants. • The number of infected and hospitalized children increased after the appearance of the Omicron variants. What is New: • Seroprevalence of SARS-CoV-2 in children of Southern Switzerland increased overtime. • Children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants in the fourth wave compared to children infected in the first three waves.

Atypical primary varicella rash: Systematic literature review.

AIM: In previously healthy subjects, primary varicella presents with a distinctive vesicular rash that is more intense on the trunk and head than on the extremities. However, an atypical presentation may occasionally develop. We aimed at systematically assessing the characteristics of cases affected by atypical primary varicella rash. METHODS: The United States National Library of Medicine, Excerpta Medica and Web of Science databases were reviewed, without date or language restrictions. Articles were eligible if reporting previously healthy and immunocompetent subjects with a primary varicella rash (i.e., a photo-localised primary varicella or skin inflammation-associated primary varicella). RESULTS: Thirty-eight reports providing information on 59 cases of atypical primary varicella were identified. Twenty-four cases (median 8.5 years of age, 19 females) were photo-localised and 35 (median 4.8 years of age, 15 females) were associated with pre-existing skin inflammation (including cast occlusion, diaper irritation, operative sites, burns, insect bites, vaccinations or pre-existing skin disease). The skin rash was monomorphic and without a "starry sky" appearance. CONCLUSION: Primary varicella may have a modified presentation in areas of irritation such as sun exposure or pre-existing inflammation. There is a need for a wider awareness of these modulators of varicella rash.

Screening for cervical cancer in Africa: A proposal of a different combination of VIA test and cervical smear in Uganda.

OBJECTIVE: To evaluate the efficacy of visual inspection with acetic acid (VIA) screening combined with a cervical smear in Uganda. METHODS: Nine screening campaigns were held in Uganda between January 2011 and October 2019. In the last three campaigns, a new approach was used: the cervical smear was performed before the VIA test and, in case of a positive VIA test, the slide was sent for examination. The data collected were divided into two groups: the first six campaigns and the last three campaigns. RESULTS: During the study period, 10 520 women were screened, of whom 911 had a positive VIA test. The VIA test showed 84.2% false positives. In the first group, the VIA test was positive in 516 women, of whom 93% were referred for further examinations. In the second group, the VIA test was positive in 395 women, but the cervical smear was positive in only 65 women. Thus, only 16.5% women were referred for further examinations. CONCLUSION: Combining cervical smear, VIA test, and slide analysis in positive VIA tests may allow women who need treatment to be selected more effectively, while waiting for other more expensive solutions to become more affordable for this setting.

Diagnosis and Treatment of Breast Cancer in Young Women.

OPINION STATEMENT: Despite the increase of breast cancer incidence with age, approximately 7 to 10% ofwomen diagnosed with breast cancer are younger than the age 40. This subgroup ofpatients has different risk factors, tumour biology, clinical outcomes, and specific psy- chosocial issues, such as fertility preservation, family planning, and job reintegration. However, age alone should not be the main consideration when choosing the aggressive- ness of the treatment, as other factors must be considered, including the biologic aggressiveness of the tumour, potential long-term toxicities, and the preferences of the patient. Fertility preservation techniques should be discussed with the patient before starting any cancer treatment. Despite the significant percentage of breast cancer patients younger than age 40, fewclinical studies have specifically investigated disease characteristics and outcomes of this population, and most therapies routinely administered to these younger women were tested in older patients. Moreover, young women who have breast cancer are at a greater risk of sexual and psychological distress, and clinicians should address these issues in order to properly support patients during the long diagnostic and therapeutic journey. Consequently, it is essential to follow diagnostic and treatment guidelines specificallyaddressed to young women. Additional specific procedures should be followed to treat pregnant patients with breast cancer.

Correlation between PSA kinetics and PSMA-PET in prostate cancer restaging: A meta-analysis.

BACKGROUND: Serum prostate-specific antigen (PSA) may predict the risk of positive positron emission tomography/computed tomography with radiolabelled prostate-specific membrane antigen (PSMA-PET/CT) in patients with biochemical recurrent prostate cancer (BRPCa). However, to date, there are no clear data regarding the correlation between PSA kinetics and PSMA-PET findings. We performed a systematic review and meta-analysis to provide evidence-based data in this setting. METHODS: A comprehensive literature search of studies published through October 2018 in PubMed/MEDLINE, EMBASE and Cochrane library databases was performed. A meta-analysis to establish the detection rate (DR) of PSMA-PET using different cut-off values of PSA doubling time (PSAdt) and a pooled analysis to establish whether shorter PSAdt may predict positive PSMA-PET results was performed in patients with BRPCa. RESULTS: Twelve articles were included in the systematic review, and eight articles (including about 1400 patients) were selected for the meta-analysis. The pooled DR including 95% confidence intervals (95%CI) of PSMA-PET in restaging prostate cancer (PCa) patients was 72% (95%CI:60%-82%), increasing to 83% (95%CI:75%-90%) when PSAdt was ≤6 months and decreasing to 60% (95%CI:37%-80%) when PSAdt was >6 months, without a statistical significant difference. PSAdt ≤6 months may predict the positive result of PSMA-PET (pooled odds ratio: 3.22; 95%CI:1.17-8.88). Statistical heterogeneity among the included studies was found. CONCLUSIONS: PSA kinetics, and in particular shorter PSAdt, may be predictor of PSMA-PET positivity in patients with BRPCa. Further larger studies in this setting are warranted.

Short-term benefit of smoking cessation along with glycopirronium on lung function and respiratory symptoms in mild COPD patients: a retrospective study.

INTRODUCTION: Tobacco smoke is the leading cause of chronic obstructive pulmonary disease (COPD). Smoking cessation can change the natural history of COPD, as we know from the GOLD guidelines. Little is known about the short-term clinical and functional effects of smoking cessation treatment combined with anti-muscarinic bronchodilators. OBJECTIVE: To determine whether quitting smoking, obtained by smoking cessation treatment combined with the use of a new long-acting muscarinic antagonist bronchodilator (LAMA), can improve lung function tests and respiratory symptoms more than the use of LAMA alone. METHODS: We evaluated, in a retrospective analysis, the functional and clinical data, collected in one year, of 120 patients who were current smokers affected by mild COPD and who quit smoking using smoking cessation treatment combined with glycopirronium. We compared them with a group of 80 patients with mild COPD undergoing the same treatment but who did not quit smoking. All patients underwent functional and clinical tests at baseline and at a third-month check. MEASUREMENTS AND MAIN RESULTS: The two groups were homogeneous in terms of demographic data without significant differences. All patients used varenicline for smoking cessation. They all performed the following tests: a spirometry with detection of resistances, the 6 min walking test, haemogasanalysis, the exhaled CO test, the COPD assessment test (CAT) and finally the modified Medical Research Council test (mMRC). A significant improvement in the functional tests at the third-month check was found in both groups-quitters and non-quitters. However, a notable increase in the examined parameters was registered in the group of patients who quit smoking, in particular, we observed a significant increase at the third-month check of the parameter forced expiratory volume in 1 s (FEV1) of more than 200 ml with p < 0.001. A comparison between quitters and non-quitters revealed a major benefit derived from smoking cessation in terms of functional changes and symptom relief. In particular, not only FEV1 but also forced expiratory flow at 25%-75% of vital capacity (FEF 25-75) (p < 0.01) and CAT (p < 0.001) were found to be significantly improved in patients who quit than in patients who did not at the check time point. CONCLUSIONS: Smoking cessation treatment obtained by varenicline was confirmed as a crucial therapeutic option, especially when combined with bronchodilator in mild COPD. Patients who quit smoking could already benefit from both treatments in the short term, improving lung function and respiratory symptoms and therefore improving their quality of life.

Impact of smoking on lung cancer treatment effectiveness: a review.

Tobacco smoke contains more than 4000 detectable substances, such as polycyclic aromatic hydrocarbons, nicotine, carbon monoxide and heavy metals, which are considered powerful enzymatic inducers that have notable influence on the efficacy and tolerability of many medications through complex pharmacokinetic and pharmacodynamic interactions. As a result, adjustments of drug dosages are required in smokers, both if they continue to smoke or if they quit after smoking cessation treatment. The purpose of this review is to examine the main drug interactions with tobacco smoke clinically relevant, with a closer look on patients developing oncologic diseases.

Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey.

BACKGROUND: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. RESULTS: Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; P<0.05). CONCLUSIONS: RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.