New Insights into the Epidemiology of Vulvar Cancer: Systematic Literature Review for an Update of Incidence and Risk Factors

The aim of this review was an update of vulvar cancer incidence rates and trends and of all known and putative risk factors for the disease. The most recent incidence data were sought from official sources (WHO Cancer Incidence in Five Continents). To obtain an estimate of time trends in some areas, we compared data from Cancer Incidence in Five Continents with the few available studies that measured incidence using comparable methods. With respect to risk factors, a systematic PubMed search identified 1585 relevant articles published between 1980 and 2021. Abstracts and full texts were screened. Sixty-nine eligible original cohort and case-control studies were selected. Information was extracted using a PRISMA predesigned form. Nineteen risk factors, or risk factor categories, were investigated by two or more original studies. Solitary, unreplicated studies addressed the putative role of eight more factors. Recent advances have provided further evidence supporting the carcinogenic model centred on human papillomavirus infection with different defects of the immune function. Conversely, the model centred on the role of vulvar lichen sclerosus and the often associated differentiated vulvar intraepithelial neoplasia has continued to be epidemiologically understudied. More research on the association between these two conditions and vulvar cancer is a priority.

Prognostic Significance of the Combined Score of Plasma Fibrinogen and Neutrophil-Lymphocyte Ratio in Patients with Spontaneous Intracerebral Hemorrhage

Background. The combination of plasma fibrinogen and neutrophil to lymphocyte ratio (F-NLR) score is a novel inflammatory marker constituted by peripheral blood fibrinogen concentration and neutrophil to lymphocyte ratio. In the current study, we aim to explore the relationship between admission F-NLR score and intracerebral hemorrhage (ICH) and assess its prognostic predictive ability in ICH patients. Methods. The original cohort was consecutively recruited from August 2014 to September 2017, and the validation cohort was consecutively recruited between October 2018 and March 2020. The primary outcomes were 3-month functional outcome and 1-month mortality. All statistical analyses were performed using SPSS and R software. Results. A total of 431 and 251 ICH patients were included in original cohort and validation cohort, respectively. In the original cohort, F-NLR score could independently predict the 3-month functional outcome (adjusted OR 2.013, 95% CI 1.316-3.078, p = 0.001 ) and 1-month mortality (adjusted OR 3.036, 95% CI 1.965-4.693, p < 0.001 ). Receiver operation characteristic (ROC) analyses and predictive model comparison indicated that F-NLR score had a stronger predictive ability in the 3-month outcome and 1-month mortality. Validation cohort verified the results. Conclusion. F-NLR score was an independent indicator for both the 3-month functional outcome and 1-month mortality, and its prognostic predictive ability was superior to fibrinogen and NLR in both the original and the validation cohort.

VEXAS syndrome with cutaneous nodules

Recently, a rare severe autoinflammatory Vacuoles, E1 enzyme, X-linked, autoinflammatory, Somatic (VEXAS) syndrome caused by somatic variants in the UBA1 gene was discovered. The clinical features of VEXAS syndrome are heterogeneous, including high-grade fever, polychondritis and skin lesions. In 2020, Beck DB et al described an original cohort of 25 patients, of whom 22 (88%) had cutaneous findings, namely, neutrophilic dermatitis, and vasculitis. We report a case of VEXAS syndrome and cutaneous nodules with confirmed UBA1 mutation.

Distinguishing COVID-19 infection and vaccination history by T cell reactivity

SARS-CoV-2 infection and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of two new pools of Experimentally-defined T cell epitopes derived from the non-spike Remainder of the SARS-CoV-2 proteome (CD4RE and CD8RE). The combination of T cell responses to these new pools and Spike (S) were used to discriminate four groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status: non-infected, non-vaccinated (I-V-); infected and non-vaccinated (I+V-); infected and then vaccinated (I+V+); and non-infected and vaccinated (I-V+). The overall classification accuracy based on 30 subjects/group was 89.2% in the original cohort and 88.5% in a validation cohort of 96 subjects. The T cell classification scheme was applicable to different mRNA vaccines, and different lengths of time post-infection/post-vaccination. T cell responses from breakthrough infections (infected vaccinees, V+I+) were also effectively segregated from the responses of vaccinated subjects using the same classification tool system. When all five groups where combined, for a total of 239 different subjects, the classification scheme performance was 86.6%. We anticipate that a T cell-based immunodiagnostic scheme able to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccination and aid in establishing SARS-CoV-2 correlates of protection.

Permanence

This chapter considers how far the Barnardos adoptees achieved legal, residential and emotional permanence after adoption. It draws on minimal follow-up data, available for 124 adoptees (59% of the original cohort); extensive data collected through responses to an online survey concerning 93 adoptees (44% of the cohort) 5–37 years after placement; and interviews focusing on 24 adult adoptees. Ages at follow-up ranged from 5 to 44. All adoptees had achieved legal permanence. Many had achieved residential permanence after numerous placements in care: 34% of those aged 18 or over were still living with their adoptive parents. Twelve (13%) placements had disrupted, but all except eight (9%) adoptees had achieved psychological permanence. Relationships between adoptees and adoptive parents were twice as likely to persist as those between care leavers and foster parents.

Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19

BACKGROUND: Due to the dissemination of vaccination against severe acute respiratory syndrome coronavirus 2 in the elderly, the virus-susceptible subjects have shifted to unvaccinated non-elderlies. The risk factors of COVID-19 deterioration in non-elderly patients without respiratory failure have not yet been determined. This study was aimed to create simple predicting method to identify such patients who have high risk for exacerbation. METHODS: We analyzed the data of 1675 patients aged under 65 years who were admitted to hospitals with mild-to-moderate COVID-19. For validation, 324 similar patients were enrolled. Disease progression was defined as administration of medication, oxygen inhalation and mechanical ventilator starting one day or longer after admission. RESULTS: The patients who exacerbated tended to be older, male, had histories of smoking, and had high body temperatures, lower oxygen saturation, and comorbidities such as diabetes/obesity and hypertension. Stepwise logistic regression analyses revealed that comorbidities of diabetes/obesity, age ≥ 40 years, body temperature ≥ 38 degree, and oxygen saturation < 96% (DOATS) were independent risk factors of worsening COVID-19. As a result two predictive scores were created: DOATS score, which includes all the above risk factors; and DOAT score, which includes all factors except for oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve of the DOATS and DOAT scores were 0.789 and 0.771, respectively. In the validation, the areas were 0.702 and 0.722, respectively. CONCLUSION: We established two simple prediction scores that can quickly evaluate the risk of progression of COVID-19 in non-elderly, mild/moderate patients.

Modeling Brain–Heart Crosstalk Information in Patients with Traumatic Brain Injury

Background Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality.. Methods In our previous work, we introduced a novel measure of brain–heart interaction termed brain–heart crosstalks (ctnp), as well as two additional brain–heart crosstalks indicators [mutual information ($$mi_{ct}$$ m i ct ) and average edge overlap (ωct)] obtained through a complex network modeling of the brain–heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package. Results A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain–heart crosstalks varied (mean 58, standard deviation 57). The Kruskal–Wallis test comparing brain–heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for $$mi_{ct}$$ m i ct , 0.005 for ctnp and 0.006 for ωct). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: − 0.13 for ctnp (p value 0.04), − 0.19 for ωct (p value 0.002969) and − 0.09 for $$mi_{ct}$$ m i ct (p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16–29, 30–49, 50–65, and 65–85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16–29, 50–65, and 65–85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain–heart crosstalks and mortality was also confirmed. Conclusions The presence of a negative relationship between mortality and brain–heart crosstalks indicators suggests that a healthy brain–cardiovascular interaction plays a role in TBI.

Prognostic Significance of Admission Systemic Inflammation Response Index in Patients With Spontaneous Intracerebral Hemorrhage: A Propensity Score Matching Analysis

Intracerebral hemorrhage (ICH) accounts for ~15% of all strokes and is associated with high mortality and disability rates. The systemic inflammation response index (SIRI) is a novel systemic inflammatory marker based on peripheral neutrophil, monocyte, and lymphocyte counts. This study aimed to evaluate the prognostic significance of admission SIRI in patients with spontaneous ICH and compare its predictive ability with that of the neutrophil-to-lymphocyte ratio (NLR). This retrospective study was conducted based on a prospectively collected database of patients with ICH between June 2016 and January 2019. Propensity score matching (PSM) was conducted to adjust for potential imbalances in the clinical parameters. A total of 403 patients were included in the original cohort. The optimal SIRI cut-off value was 2.76. After 1:1 PSM based on potential confounding variables, a new cohort containing 262 patients was established for further analysis. In the original cohort, SIRI served as an independent predictor of 3-month functional outcome [odds ratio (OR), 1.302; 95% CI, 1.120–1.512; p = 0.001] and 1-month mortality (OR, 1.072; 95% CI, 1.020–1.126; p = 0.006), while NLR was independently associated with only 3-month functional outcomes (OR, 1.051; 95% CI, 1.004–1.100; p = 0.031) and not 1-month mortality. The same applied to the PSM cohort. Receiver operating characteristic analyses and predictive models indicated that in most instances, SIRI was superior to NLR and their components in predicting the outcomes of patients with ICH. Our study found that SIRI is determined to be an independent predictive indicator for ICH patients in 3-month functional outcomes and 1-month mortality. The prognostic predictive ability of SIRI was stronger than that of NLR.

Heart-Ankle Pulse Wave Velocity Is Superior to Brachial-Ankle Pulse Wave Velocity in Detecting Aldosterone-Induced Arterial Stiffness

Primary aldosteronism (PA) is associated with higher arterial stiffness compared to essential hypertension (EH). However, few studies have compared different pulse wave velocity (PWV) parameters to detect aldosterone-induced arterial stiffness. In this study, we aimed to compare the sensitivity in detecting aldosterone-induced arterial stiffness between brachial-ankle PWV (baPWV) and heart-ankle PWV (haPWV). We prospectively enrolled 1006 PA patients and 983 EH patients. Detailed medical history, basic biochemistry data and two PWV measurements (baPWV and haPWV) were collected in both groups. We performed analysis on the original cohort and two propensity score matching (PSM) models (model 1 adjusted for age and sex; model 2 adjusted for age, sex, systolic and diastolic blood pressure). The DeLong test was used to compare areas under receiver operating characteristic curves (AUCs) between baPWV and haPWV to predict PA. In all models, the PA patients had significantly higher baPWV compared to the EH patients. The AUC of haPWV was greater than that of baPWV. In conclusion, haPWV seems to be a better PWV parameter than baPWV in detecting aldosterone-induced arterial stiffness.

The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study

Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited.Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression‐free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups.Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS.Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.