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Background. High neutrophil to lymphocyte ratio (NLR) has shown to be a predictor of poor outcomes in various malignancies, including pancreatic cancer. Methods. We assessed 70 consecutive pts with histologically confirmed mPC who received chemotherapy with nab-paclitaxel/gemcitabine at two different European oncologic centers between January 2012 and November 2015. Variables assessed for prognostic correlations included age ≥ 66, sex, Karnofsky PS score, primary tumor site, baseline CA19.9 level ≥ 59xULN, 12-week decrease of the CA19.9 level ≥ 50% from baseline, basal bilirubin level, baseline NLR, biliary stent implantation, and liver metastasis. Survival analyses were generated according to the Kaplan-Meier method. Univariate and multivariate analyses were performed by a Cox proportional hazard model. Results. According to NLR values, the patients were divided into two groups: high and low. Low group patients showed a better median PFS (7 months versus 5 months) and median OS (13 months versus 7 months) in respect to high group patients. At multivariate analysis, Karnofsky PS

Importance: A diagnosis of bacterial meningitis in childhood can lead to permanent neurological disabilities. Few studies have examined long-term consequences for work ability in adulthood., Objective: To compare earnings, work loss, and educational attainment between adults diagnosed with bacterial meningitis in childhood and population comparators., Design, Setting, and Participants: This nationwide registry-based matched cohort study included individuals in Sweden diagnosed with bacterial meningitis in childhood (aged <18 years) from January 1, 1987, to December 31, 2019, and general population comparators matched 1:9 on age, sex, and place of residence. Follow-up was completed December 31, 2020. Data were analyzed from February 7 to September 12, 2023., Exposure: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register., Main Outcomes and Measures: Annual taxable earnings (in 2020 US dollars), work loss (sum of sick leave and disability insurance), and educational attainment., Results: The cohort included 2534 individuals diagnosed with bacterial meningitis in childhood (mean [SD] age at diagnosis, 4.7 [5.3] years) and 22 806 comparators (13 510 [53.3%] male). Among those with childhood bacterial meningitis, 812 (32.0%) were diagnosed at younger than 1 year and 1351 (53.3%) were male. From 18 to 34 years of age, those with childhood meningitis had lower adjusted earnings relative to comparators and higher adjusted work loss. When pooling observations for individuals 28 years or older, the annual mean reduction in earnings was -$1295 (95% CI, -$2587 to -$4), representing a 4.0% (95% CI, 0%-8.0%) reduction relative to comparators, and the annual increase in work loss was 13.5 (95% CI, 8.6-18.5) days. There was a larger reduction in earnings for those with childhood meningitis relative to comparators with pneumococcal (Streptococcus pneumoniae) vs meningococcal (Neisseria meningitidis) meningitis. For work loss, there was a difference among all 3 major causes of meningitis, with the largest increase for pneumococcal meningitis. Individuals diagnosed at a younger age (below the median) had lower earnings relative to comparators and higher work loss than individuals diagnosed at an older age (above the median). Fewer individuals with childhood meningitis relative to comparators had obtained a high school degree at age 30 years (adjusted odds ratio, 0.68 [95% CI, 0.56-0.81])., Conclusions and Relevance: In this cohort study of adults diagnosed with bacterial meningitis in childhood, findings suggest that work ability decreases relative to population comparators, with lower earnings and higher work loss, especially among adults diagnosed with pneumococcal meningitis or diagnosed at a young age, with long-lasting costs for the individual patient and society at large.

Understanding recovery times and mechanisms of ecosystem dynamics towards the old-growth stage is crucial for forest restoration, but still poorly delineated in Mediterranean. Through tree-ring methods, we reconstructed the return of a tall canopy after severe human disturbance in a mixed beech (Fagus sylvatica) and silver fir (Abies alba) forest, located at a mountain site in the southern edge of both species' range (Gariglione, south Italy). The primary forest was extensively harvested between 1930 and 1950, removing up to 91 % of the biomass. Growth histories, climate-growth relationships and time-series of growth dominance in Gariglione were compared with a network of protected mature and old-growth beech forests distributed along a wide elevational gradient in the same region. We found that the renewed tall canopy of Gariglione is mainly composed of remnant trees, which include uncut trees and saplings, and the post-harvesting regeneration mostly represented by fir. Canopy beech trees reached maximum basal area increment (BAI) in the 1970s, 40-50 years after cutting. Then, beech BAI shifted towards negative trends in phase with drying climate (PDSI), while fir maintained a sustained growth until 2000. This growth asynchrony between the two species conferred community stability over the last decades. The network comparison highlighted the common negative impact of summer drought on high-frequency growth signals of beech in south Italy. However, analysis of long-term mean growth trends indicates decreasing BAI limited to Gariglione beech, revealing relevant differences due to site ecology and its interactions with legacy effects of past management in driving growth responses to climate change. Indeed, lowland mature beech forests showed increasing BAI in the last decades, while primary high-mountain forests displayed a remarkably stable low oscillating growth. In all the Mediterranean forests we studied, large and old trees showed a marked growth acclimation despite ongoing climate warming, demonstrating the effectiveness of landscape rewilding., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors reports financial support was provided by Sila National Park Agency. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Axillary lymph node (ALN) staging is crucial for the management of invasive breast cancer (BC). Although various radiological investigations are available, ultrasound (US) is the preferred tool for evaluating ALNs. Despite its immediacy, widespread use, and good predictive value, US is limited by intra- and inter-operator variability. This study aims to evaluate US and Elastosonography Shear Wave (SW-ES) parameters for ALN staging to develop a predictive model, named the Cassandra score (CS), to improve the interpretation of findings and standardize staging. Materials and Methods: Sixty-three women diagnosed with BC and treated at two Italian hospitals were enrolled in the study. A total of 529 lymph nodes were surgically removed, underwent intraoperative US examination, and were individually sent for a final histological analysis. The study aimed to establish a direct correlation between eight US-SWES features (margins, vascularity, roundness index (RI), loss of hilum fat, cortical thickness, shear-wave elastography hardness (SWEH), peripheral infiltration (PI), and hypoechoic appearance) and the histological outcome (benign vs. malignant). Results: Several statistical models were compared. PI was strongly correlated with malignant ALNs. An ROC analysis for Model A revealed an impressive AUC of 0.978 (S.E. = 0.007, p < 0.001), while in Model B, the cut-offs of SWEH and RI were modified to minimize the risk of false negatives (AUC of 0.973, S.E. = 0.009, p < 0.001). Model C used the same cut-offs as Model B, but excluded SWEH from the formula, to make the Cassandra model usable even if the US machine does not have SW-ES capability (AUC of 0.940, S.E. = 0.015, p < 0.001). A two-tiered model was finally set up, leveraging the strong predictive capabilities of SWEH and RI. In the first tier, only SWES and RI were evaluated: a positive result was predicted if both hardness and roundness were present (SWES > 137 kPa and RI < 1.55), and conversely, a negative result was predicted if both were absent (SWES < 137 kPa and RI > 1.55). In the second tier, if there was a mix of the results (SWES > 137 kPa and RI > 1.55 or SWES < 137 kPa and RI < 1.55), the algorithm in Model B was applied. The model demonstrated an overall prediction accuracy of 90.2% in the training set, 87.5% in the validation set, and 88.9% across the entire dataset. The NPV was notably high at 99.2% in the validation set. This model was named the Cassandra score (CS) and is proposed for the clinical management of BC patients. Conclusion: CS is a simple, non-invasive, fast, and reliable method that showed a PPV of 99.1% in the malignancy prediction of ALNs, potentially being also well suited for young sonographers.

The global healthcare sector faced immense challenges due to the COVID-19 pandemic. Oncologists noted reduced cancer screening, which impacted melanoma diagnosis and treatment, leading to concerns about delayed care and poorer outcomes. This review analyzes how the pandemic influenced melanoma ulceration risk and Breslow thickness index through a meta-analysis of published studies. Following PRISMA guidelines, we conducted a systematic review of literature from January 2021 to December 2022 on cutaneous melanoma before and during the COVID-19 pandemic. Upon screening 1854 manuscripts, the review led to 13 studies meeting inclusion standards. The quality assessment followed MINORS and Newcastle-Ottawa Scale criteria. Regarding ulceration, post-COVID ulceration surpassed pre-COVID levels significantly, with a risk ratio of 1.31 and an estimated odds ratio of 1.41, indicating a 44% rise post-COVID. As for Breslow thickness, studies show a rising trend in the Breslow index post-COVID, but less significantly, with an effect size of 0.08 regarding the meta-analysis model (P = 0.02) with a pre-COVID mean Breslow of 1.56 mm and post-COVID of 1.84 mm. This meta-analysis concluded that post-COVID ulceration rates significantly surpassed pre-COVID levels. Considering that ulcerated melanomas usually undergo sentinel lymph node biopsy and are more likely to benefit from adjuvant therapies, this indicates important implications, as many patients might have missed the opportunity to start therapy appropriately, regardless of their Breslow thickness status., (© 2024 the International Society of Dermatology.)

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by a neuroinflammatory response and the deleterious action of bacterial toxins in the brain. However, little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-derived meningitis mouse model, we combined 3D whole brain imaging with brain microdissection to show that all brain regions were equally affected during disease progression, with the presence of pneumococci closely associated to the microvasculature. In the hippocampus, the invasion provoked microglial activation, while the neurogenic niche showed increased proliferation and migration of neuroblasts. Our results indicate that, even before the outbreak of symptoms, the bacterial load throughout the brain is high and causes neuroinflammation and cell death, a pathological scenario which ultimately leads to a failing regeneration of new neurons., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Bacterial meningitis, frequently caused by Streptococcus pneumoniae (pneumococcus), represents a substantial global health threat leading to long-term neurological disorders. This study focused on the cholesterol-binding toxin pneumolysin (PLY) released by pneumococci, specifically examining clinical isolates from patients with meningitis and comparing them to the PLY-reference S. pneumoniae strain D39. Clinical isolates exhibit enhanced PLY release, likely due to a significantly higher expression of the autolysin LytA. Notably, the same single amino acid (aa) D380 substitution in the PLY D4 domain present in all clinical isolates significantly enhances cholesterol binding, pore-forming activity, and cytotoxicity toward SH-SY5Y-derived neuronal cells. Scanning electron microscopy of human neuronal cells and patch clamp electrophysiological recordings on mouse brain slices confirm the enhanced neurotoxicity of the PLY variant carrying the single aa substitution. This study highlights how a single aa modification enormously alters PLY cytotoxic potential, emphasizing the importance of PLY as a major cause of the neurological sequelae associated with pneumococcal meningitis., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background : Breast localization plays a key role in early breast cancer (BC) surgery. The current gold standard is wire-guided localization (WGL), despite the known disadvantages. The patients often experience anxiety and discomfort due the metallic wire placed in the breast, and surgeons are compelled to perform the surgery on the same day as the radiological release of the wire to prevent migrations or breakages. Various wireless systems have been proposed as alternative to WGL. LOCalizer TM offers the advantage of providing the exact distance from the marker called Tag. The combined technique using LOCalizer TM and US allows for determining the distance from the BC margin, a critical surgical goal for oncological radicality. Methods : Patients referred for breast surgery to two Italian hospitals were enrolled and divided into two groups: Group A, including patients undergoing a combined approach, and group B, including patients treated with conventional WGL. Results : The combined approach with LOCalizer TM and US was associated with better outcomes in terms of oncological radicality, cosmetic results, and patients' satisfaction. Conclusions : In the current study, LOCalizer TM associated with US could be considered an excellent approach for localizing non-palpable BC. Further larger comparative studies are needed to address this issue.

Background. Obesity is a prevalent condition associated with various comorbidities, impacting mortality, fertility, and quality of life. Its relationship with type 2 diabetes mellitus (DMII) is well established, with nearly 44% prevalence. Bariatric surgery has proven crucial for treating both obesity and DMII. The comparison between surgical techniques, such as sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB), remains controversial in terms of glycemic control efficacy. This retrospective study aimed to assess DMII remission efficacy between SG and OAGB after 36 months. Methods. From January 2016 to September 2020, 201 patients who underwent SG and OAGB for morbid obesity associated with DMII were accurately followed-up with for 36 months, focusing on %HbA1c, DMII remission, anthropometric results, and nutrient deficiency. Results. Although DMII remission did not exhibit statistical significance between the groups (82% vs. 93%, SG vs. OAGB, p = 0.051), OAGB demonstrated a more robust association with glycemic control (Odds Ratio 0.51) throughout the entire follow-up and yielded superior anthropometric outcomes. Notably, nutrient deficiencies, excluding cholecalciferol, iron, and riboflavin, did not show significant intergroup differences. Conclusions. This study contributes valuable insights into the extended-term efficacy of SG and OAGB in DMII remission. The nuanced findings underscore the multifaceted nature of metabolic outcomes, suggesting that factors beyond weight loss influence diabetes resolution. Larger comparative studies are warranted to comprehensively address this issue.

Breast angiosarcoma is a rare malignancy, accounting for less than 1% of all soft tissue cancers. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite multimodal treatment, angiosarcomas represent an incurable disease for many patients and a significant cause of deterioration in their quality of life. Surgery is a cornerstone in management, but high recurrence rates are reported. Electrochemotherapy (ECT) is a practicable locoregional treatment for patients with advanced angiosarcoma as part of a multimodal therapeutic strategy. The palliative benefits of ECT include optimal patient compliance, good local hemostasis control, and positive local responses. Since only 22 cases are described in the literature, we reported a rare case of RAS treated with ECT after a multidisciplinary approach, including Next Generation Sequencing (NGS). A literature review on the feasibility of ECT in RAS management was also performed., Competing Interests: The authors have no conflicts of interest to declare.

Importance: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort., Objective: To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden., Design, Setting, and Participants: This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023., Exposure: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021., Main Outcomes and Measures: Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood., Results: The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median., Conclusions and Relevance: The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.

Purpose : The purpose of this meta-analysis is to investigate the effectiveness of supplementing screening mammography with three-dimensional automated breast ultrasonography (3D ABUS) in improving breast cancer detection rates in asymptomatic women with dense breasts. Materials and Methods: We conducted a thorough review of scientific publications comparing 3D ABUS and mammography. Articles for inclusion were sourced from peer-reviewed journal databases, namely MEDLINE (PubMed) and Scopus, based on an initial screening of their titles and abstracts. To ensure a sufficient sample size for meaningful analysis, only studies evaluating a minimum of 20 patients were retained. Eligibility for evaluation was further limited to articles written in English. Additionally, selected studies were required to have participants aged 18 or above at the time of the study. We analyzed 25 studies published between 2000 and 2021, which included a total of 31,549 women with dense breasts. Among these women, 229 underwent mammography alone, while 347 underwent mammography in combination with 3D ABUS. The average age of the women was 50.86 years (±10 years standard deviation), with a range of 40-56 years. In our efforts to address and reduce bias, we applied a range of statistical analyses. These included assessing study variation through heterogeneity assessment, accounting for potential study variability using a random-effects model, exploring sources of bias via meta-regression analysis, and checking for publication bias through funnel plots and the Egger test. These methods ensured the reliability of our study findings. Results: According to the 25 studies included in this metanalysis, out of the total number of women, 27,495 were diagnosed with breast cancer. Of these, 211 were diagnosed through mammography alone, while an additional 329 women were diagnosed through the combination of full-field digital mammography (FFDSM) and 3D ABUS. This represents an increase of 51.5%. The rate of cancers detected per 1000 women screened was 23.25‱ (95% confidence interval [CI]: 21.20, 25.60; p < 0.001) with mammography alone. In contrast, the addition of 3D ABUS to mammography increased the number of tumors detected to 20.95‱ (95% confidence interval [CI]: 18.50, 23; p < 0.001) per 1000 women screened. Discussion: Even though variability in study results, lack of long-term outcomes, and selection bias may be present, this systematic review and meta-analysis confirms that supplementing mammography with 3D ABUS increases the accuracy of breast cancer detection in women with ACR3 to ACR4 breasts. Our findings suggest that the combination of mammography and 3D ABUS should be considered for screening women with dense breasts. Conclusions: Our research confirms that adding 3D automated breast ultrasound to mammography-only screening in patients with dense breasts (ACR3 and ACR4) significantly ( p < 0.05) increases the cancer detection rate.

Breast conservative surgery is the primary therapeutic choice for non-aggressive early breast cancers, and a minimally-invasive approach is strongly recommended. The breast localization represents a modern challenge for surgery. Wire-guided localization is still the gold standard technique, but new wireless systems have been proposed, such as radiofrequency identification with LOCalizer TM (Hologic, Santa Carla, CA, USA), which reports encouraging results. The current study aimed to evaluate the accuracy and efficacy of the combined use of LOCalizer TM and ultrasound compared with the results obtained using LOCalizer TM alone for the detection of non-palpable breast cancer. Ninety-six patients who were candidates for breast localization were enrolled. Group A received a combined localization with LOCalizer TM and US, while group B underwent only LOCalizer TM identification. Oncological radicality was reached in 100% of the patients in Group A and in 89.2% of the patients in Group B, with p = 0.006. The mean specimens' volume was 13.2 ± 0.6 cm 3 for Group A and 16.1 ± 1.4 cm 3 for Group B, while mean specimen weights were 21.8 ± 2.2 and 24.4 ± 1.8 g, respectively ( p = 0.003 and p = 0.004, respectively). LOCalizer TM with ultrasound, in the current series, has resulted in the preferred option for the localization of non-palpable breast cancer, allowing limited resection (in weight and volume), guaranteeing excellent oncological outcomes, and great satisfaction for patients and physicians.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group B Streptococcus) , Escherichia coli , and Staphylococcus aureus are neonatal meningitis's most common causal agents. Despite efforts to vaccinate against the most common causes of bacterial neuro-infections, bacterial meningitis remains a significant cause of mortality and morbidity in Africa, with children below 5 years bearing the heaviest disease burden. The factors attributed to this continued high disease burden include poor infrastructure, continued war, instability, and difficulty in diagnosis of bacterial neuro-infections leading to delay in treatment and hence high morbidity. Despite having the highest disease burden, there is a paucity of African data on bacterial meningitis. In this article, we discuss the common etiologies of bacterial neuroinfectious diseases, diagnosis and the interplay between microorganisms and the immune system, and the value of neuroimmune changes in diagnostics and therapeutics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barichello, Rocha Catalão, Rohlwink, Kuip, Zaharie, Solomons, van Toorn, Tutu van Furth, Hasbun, Iovino and Namale.)

Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in about 14−54% of invasive breast cancers, but its prognostic value in clinical practice is still unclear. Methods: In order to investigate the relationship between c-MET expression levels and prognosis, we retrospectively reviewed the clinical features and outcomes of 105 women with estrogen receptor positive HER2 negative (ER+/HER2-) resected breast cancer. We used the Kaplan Meier method to estimate Disease Free Survival (DFS) and Breast Cancer Specific Survival (BCSS) in the subgroups of patients with high (≥50%) and low (<50%) c-MET expression. Univariate and multivariate Cox proportional regression models were performed to assess the prognostic impact of clinicopathological parameters for DFS an BCSS. Results: High c-MET values significantly correlated with tumor size, high Ki67 and low (<20%) progesterone receptor expression. At a median follow up of 60 months, patients with high c-MET tumor had significantly worse (p = 0.00026) and BCSS (p = 0.0013). Univariate analysis showed a significant association between large tumor size, elevated Ki67, c-MET values and increased risk of recurrence or death. The multivariate COX regression model showed that tumor size and high c-MET expression were independent predictors of DFS (p = 0.019 and p = 0.022). Moreover, large tumor size was associated with significantly higher risk of cancer related death at multivariate analysis (p = 0.017), while a trend towards a poorer survival was registered in the high c-MET levels cohort (p = 0.084). Conclusions: In our series, high c-MET expression correlated with poor survival outcomes. Further studies are warranted to validate the clinical relevance and applicability of c-MET as a prognostic factor in ER+/HER2- early BC.

Pneumococcal meningitis, inflammation of the meninges due to an infection of the Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is the most common form of community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal fluid (CSF), which is important for the clearance of waste away from the brain. Wistar rats, subjected to either pneumococcal meningitis or artificial CSF (sham control), received Evans blue-albumin (EBA) intracisternally. Overall, the meningitis group presented a significant impairment of the glymphatic system by retaining the EBA in the CSF compartments compared to the uninfected sham group. Our results clearly showed that during pneumococcal meningitis, the glymphatic system does not function because of a detachment of the astrocytic end feet from the blood-brain barrier (BBB) vascular endothelium, which leads to misplacement of AQP4 with the consequent loss of the AQP4 water channel's functionality. IMPORTANCE The lack of solute drainage due to a dysfunctional glymphatic system leads to an increase of the neurotoxic bacterial material in the CSF compartments of the brain, ultimately leading to brain-wide neuroinflammation and neuronal damage with consequent impairment of neurological functions. The loss of function of the glymphatic system can therefore be a leading cause of the neurological sequelae developing post-bacterial meningitis.

Pneumococcal conjugate vaccines (PCVs) used in childhood vaccination programs have resulted in replacement of vaccine-type with nonvaccine-type pneumococci in carriage and invasive pneumococcal disease (IPD). A vaccine based on highly conserved and protective pneumococcal antigens is urgently needed. Here, we performed intranasal immunization of mice with pneumococcal membrane particles (MPs) to mimic natural nasopharyngeal immunization. MP immunization gave excellent serotype-independent protection against IPD that was antibody dependent but independent of the cytotoxin pneumolysin. Using Western blotting, immunoprecipitation, mass spectrometry, and different bacterial mutants, we identified the conserved lipoproteins MalX and PrsA as the main antigens responsible for cross-protection. Additionally, we found that omitting the variable surface protein and vaccine candidate PspA from MPs enhanced protective immune responses to the conserved proteins. Our findings suggest that MPs containing MalX and PrsA could serve as a platform for pneumococcal vaccine development targeting the elderly and immunocompromised.

Magnetic resonance imaging (MRI) offers excellent spatial and contrast resolution for evaluating a wide variety of pathologies, without exposing patients to ionizing radiations. Additionally, MRI offers reproducible diagnostic imaging results that are not operator-dependent, a major advantage over ultrasound. MRI is commonly used in pregnant women to evaluate, most frequently, acute abdominal and pelvic pain or placental abnormalities, as well as neurological or fetal abnormalities, infections, or neoplasms. However, to date, our knowledge about MRI safety during pregnancy, especially about the administration of gadolinium-based contrast agents, which are able to cross the placental barrier, is still limited, raising concerns about possible negative effects on both the mother and the health of the fetus. Contrast agents that are unable to cross the placenta in a way that is safe for the fetus are desirable. In recent years, some preclinical studies, carried out in rodent models, have evaluated the role of long circulating liposomal nanoparticle-based blood-pool gadolinium contrast agents that do not penetrate the placental barrier due to their size and therefore do not expose the fetus to the contrast agent during pregnancy, preserving it from any hypothetical risks. Hence, we performed a literature review focusing on contrast and non-contrast MRI use during pregnancy.

Bacterial meningitis is an inflammation of the meninges which covers and protects the brain and the spinal cord. Such inflammation is mostly caused by blood-borne bacteria that cross the blood-brain barrier (BBB) and finally invade the brain parenchyma. Pathogens such as Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae are the main etiological causes of bacterial meningitis. After trafficking across the BBB, bacterial pathogens in the brain interact with neurons, the fundamental units of Central Nervous System, and other types of glial cells. Although the specific molecular mechanism behind the interaction between such pathogens with neurons is still under investigation, it is clear that bacterial interaction with neurons and neuroinflammatory responses within the brain leads to neuronal cell death. Furthermore, clinical studies have shown indications of meningitis-caused dementia; and a variety of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease are characterized by the loss of neurons, which, unlike many other eukaryotic cells, once dead or damaged, they are seldom replaced. The aim of this review article is to provide an overview of the knowledge on how bacterial pathogens in the brain damage neurons through direct and indirect interactions, and how the neuronal damage caused by bacterial pathogen can, in the long-term, influence the onset of neurodegenerative disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Farmen, Tofiño-Vian and Iovino.)

Neuronal damage is a major consequence of bacterial meningitis, but little is known about mechanisms of bacterial interaction with neurons leading to neuronal cell death. Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis and many survivors develop neurological sequelae after the acute infection has resolved, possibly due to neuronal damage. Here, we studied mechanisms for pneumococcal interactions with neurons. Using human primary neurons, pull-down experiments and mass spectrometry, we show that pneumococci interact with the cytoskeleton protein β-actin through the pilus-1 adhesin RrgA and the cytotoxin pneumolysin (Ply), thereby promoting adhesion and invasion of neurons, and neuronal death. Using our bacteremia-derived meningitis mouse model, we observe that RrgA- and Ply-expressing pneumococci co-localize with neuronal β-actin. Using purified proteins, we show that Ply, through its cholesterol-binding domain 4, interacts with the neuronal plasma membrane, thereby increasing the exposure on the outer surface of β-actin filaments, leading to more β-actin binding sites available for RrgA binding, and thus enhanced pneumococcal interactions with neurons. Pneumococcal infection promotes neuronal death possibly due to increased intracellular Ca2+ levels depending on presence of Ply, as well as on actin cytoskeleton disassembly. STED super-resolution microscopy showed disruption of β-actin filaments in neurons infected with pneumococci expressing RrgA and Ply. Finally, neuronal death caused by pneumococcal infection could be inhibited using antibodies against β-actin. The generated data potentially helps explaining mechanisms for why pneumococci frequently cause neurological sequelae., Competing Interests: The authors have declared that no competing interests exist.

The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.

Cholesterol-dependent cytolysins (CDCs) are essential virulence factors for many human pathogens like Streptococcus pneumoniae (pneumolysin, PLY), Streptococcus pyogenes (streptolysin O, SLO), and Listeria monocytogenes (Listeriolysin, LLO) and induce cytolysis and inflammation. Recently, we identified that pneumococcal PLY interacts with the mannose receptor (MRC-1) on specific immune cells thereby evoking an anti-inflammatory response at sublytic doses. Here, we identified the interaction sites between MRC-1 and CDCs using computational docking. We designed peptides from the CTLD4 domain of MRC-1 that binds to PLY, SLO, and LLO, respectively. In vitro, the peptides blocked CDC-induced cytolysis and inflammatory cytokine production by human macrophages. Also, they reduced PLY-induced damage of the epithelial barrier integrity as well as blocked bacterial invasion into the epithelium in a 3D lung tissue model. Pre-treatment of human DCs with peptides blocked bacterial uptake via MRC-1 and reduced intracellular bacterial survival by targeting bacteria to autophagosomes. In order to use the peptides for treatment in vivo, we developed calcium phosphate nanoparticles (CaP NPs) as peptide nanocarriers for intranasal delivery of peptides and enhanced bioactivity. Co-administration of peptide-loaded CaP NPs during infection improved survival and bacterial clearance in both zebrafish and mice models of pneumococcal infection. We suggest that MRC-1 peptides can be employed as adjunctive therapeutics with antibiotics to treat bacterial infections by countering the action of CDCs., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Fluorescence in vitro bioimaging suffers from photobleaching of organic dyes, thus, functional probes with superior photostability are urgently needed. Here, we address this challenge by developing novel silica-coated nanophosphors that may serve as superior luminescent nanoprobes compatible with conventional fluorescence microscopes. We specifically explore their suitability for dynamic in vitro bioimaging of interactions between bacterial pathogens and host cells, and further demonstrate the facile surface functionalization of the amorphous silica layer with antibodies for selective cell targeting.

Background: The aim of the present study is to investigate the role of the colonization of suture thread to identify patients at risk of developing a surgical site infection (SSI) after clean surgical procedures. Methods: Patients who underwent elective clean surgery procedures at the Surgery Unit of the AOU-University of Campania Luigi Vanvitelli in a 21-month period were prospectively enrolled. For each patient, a synthetic absorbable thread in Lactomer 9-1 was inserted into the surgical site at the end of surgery and microbiologically evaluated after 48 h. Antibiotic prophylaxis was chosen according to international guidelines. Results: A total of 238 patients were enrolled; 208 (87.4%) of them were subjected to clean procedures without the placement of prosthesis, and 30 (12.6%) with prosthesis. Of the 238 patients, 117 (49.2%) underwent an antimicrobial prophylaxis. Overall, 79 (33.2%) patients showed a bacterial colonization of the thread: among the 208 without the implantation of prosthesis, 19 (21.8%) of the 87 with antibiotic prophylaxis and in 58 (47.9%) of the 121 without it; among the 30 patients with the implantation of prosthesis, only two patients showed a colonized thread. The patients with antibiotic prophylaxis developed a colonization of the thread less frequently than those without it (17.9% vs. 47.9%, p < 0.001). SSI was observed in six (2.5%) patients, all of them showing a colonized thread (7.6% vs. 0%, p < 0.001). The bacteria identified in colonized threads were the same as those found in SSIs. Conclusions: Our study presents a new method that is able to precociously assess patients who have undergone clean procedures who may develop SSI, and identify the microorganism involved.

After almost 40 years, the 27 member states (MS) of the European Union (EU) will comply with the European Law 429/2016 in 2021 by completing a process of unification and harmonization of all regulations related to animal health between MS. These new provisions are based on modern scientific principles on animal health, on long-term epidemiological data, and, above all, on the most current risk assessment and analysis. The paper describes all changes and updates, which will impact the Italian current National regulation. A total of 58 animal diseases have been included in the Annex II ("Listing") and Annex IV ("Categorization") of the new Delegated Act (DA 2018/1629). Five diseases comprising the great viral epizooties were automatically included on the list because of their primary importance. These diseases include foot and mouth disease (FMD), African swine fever (ASF), classical swine fever (CSF), highly pathogenic avian influenza (HPAI), and African horse sickness (AHS). Another 53 diseases have been identified by the ad hoc assessment on listing and categorization of animal diseases developed by the European Food Safety Association. Seventeen communicable diseases of the Order Artiodactlya (sheep, goats, deer, etc.) have been listed including foot and mouth disease, sheep and goat pox, and pestes de petits ruminants. In addition, other endemic diseases affecting more than one species include blue tongue, tuberculosis, brucellosis, and anthrax. There are five categories (A-E) based on the degree of action to be undertaken throughout the EU for each disease. These vary from complete eradication for diseases not normally found in the EU like FMD (category A) for establishing surveillance for diseases like West Nile that present high risk but lack control tools (category E).

Objective: Anaplastic lymphoma kinase (ALK) gene has been demonstrated to be rearranged, mutated or amplified in several haematological and solid tumors. Moreover, the use of ALK inhibitors has recently revolutionized the treatment of ALK-rearranged patients affected by non-small cell lung carcinoma. Herein we review the genetic alterations of ALK in melanocytic neoplasms described in literature, focusing on their potential diagnostic and predictive role., Materials and Methods: The Authors reviewed the pertinent literature through research on PubMed server was performed typing the terms "ALK", "Anaplastic lymphoma kinase", "ALKATI", "Melanoma", "Spitz", "Spitzoid"., Results: ALK translocations were demonstrated in melanocytic neoplasms, particularly in acral melanoma and spitzoid tumors. ALKATI was described in primary and metastatic melanoma, indicating its early occurrence in oncogenesis, with varying immunohistochemical expression of the protein., Conclusions: The identification of the specific type of ALK mutations could be interesting for planning biologic therapy of melanoma patients. Further studies are needed to evaluate the possibility to introduce an ALK-targeted therapy in patients affected by malignant melanoma.

The Gram-positive bacterium Streptococcus pneumoniae, the pneumococcus, is an important commensal resident of the human nasopharynx. Carriage is usually asymptomatic, however, S. pneumoniae can become invasive and spread from the upper respiratory tract to the lungs causing pneumonia, and to other organs to cause severe diseases such as bacteremia and meningitis. Several pneumococcal proteins important for its disease-causing capability have been described and many are expressed on the bacterial surface. The surface located pneumococcal type-1 pilus has been associated with virulence and the inflammatory response, and it is present in 20%-30% of clinical isolates. Its tip protein RrgA has been shown to be a major adhesin to human cells and to promote invasion through the blood-brain barrier. In this review we discuss recent findings of the impact of RrgA on bacterial colonization of the upper respiratory tract and on pneumococcal virulence, and use epidemiological data and genome-mining to suggest trade-off mechanisms potentially explaining the rather low prevalence of pilus-1 expressing pneumococci in humans., (© 2020 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Molecular profiling of a tumor allows the opportunity to design specific therapies which are able to interact only with cancer cells characterized by the accumulation of several genomic aberrations. This study investigates the usefulness of next-generation sequencing (NGS) and mutation-specific analysis methods for the detection of target genes for current therapies in non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and melanoma patients. We focused our attention on EGFR, BRAF, KRAS, and BRAF genes for NSCLC, melanoma, and mCRC samples, respectively. Our study demonstrated that in about 2% of analyzed cases, the two techniques did not show the same or overlapping results. Two patients affected by mCRC resulted in wild-type (WT) for BRAF and two cases with NSCLC were WT for EGFR according to PGM analysis. In contrast, these samples were mutated for the evaluated genes using the therascreen test on Rotor-Gene Q. In conclusion, our experience suggests that it would be appropriate to confirm the WT status of the genes of interest with a more sensitive analysis method to avoid the presence of a small neoplastic clone and drive the clinician to correct patient monitoring., Competing Interests: The authors declare no conflict of interest.

Background: Cutaneous melanoma is one of the most severe skin diseases. Nodular melanoma is the second melanoma subtype in order of frequency. The prognosis of skin melanoma depends on the vertical growth of the tumor (Breslow index). For this measurement, excisional biopsy is strongly recommended. This is, however, an invasive procedure and may cause damage to the lymphatic drainage system. The HFUS system, , can be extremely useful for determining tumor thickness in the preoperative phase, given its high resolution capacity. The aim of this preliminary study is to define the role of HFUS for the nodular skin melanoma Breslow thickness in adults before surgery by making a comparison with histological features., Methods: In this study, 14 melanocytic lesions (8 male and 6 female) were evaluated with dermatoscopic clinical features strongly indicative of nodular melanoma. Out of these, excisional biopsy of 7 lesions was requested. The ultrasounds were performed preoperatively. The images were acquired through the first ultrasound scanner with ultra-high frequency probes (range from 50MHz to 70 MHz) available on the market under the EEC mark (Vevo "MD, FUJIFILM Visual Sonics, Amsterdam, the Netherlands) equipped with a linear probe of 50-70 MHz., Results: From the ultrasonographic analysis of 14 nodular melanoma thickness was determined for the presence of two hyperechogenic laminae, separated by a hypo / anechoic space. The twelve lesions were in situ while the other two lesions showed ultrasonography for example; the satellite lesions (less than two centimeters from the primary lesion) and in transit (localizable to more than two centimeters from the primary lesion). Four of these lesions were ulcerated. A comparsion was made the 7 lesions on between the thickness calculated with this method, and that obtained on the bioptic piece. The presence of a positive concordance has been evident in all of the cases., Conclusion: If further studies are needed to support its widespread clinical use, its is believed that, in expert hands and with an interdisciplinary team, HFUS is already capable to reliably calculate a Breslow index in a large majority of patients with cutaneous melanoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-localize with estrogen receptors (ERs), suggesting the potential use of hybrid (epi)molecules to target histone methylation and therefore regulate/redirect hormone receptor signaling. Here, we report on the biological activity of a dual-KDM inhibitor (MC3324), obtained by coupling the chemical properties of tranylcypromine, a known LSD1 inhibitor, with the 2OG competitive moiety developed for JmjC inhibition. MC3324 displays unique features not exhibited by the single moieties and well-characterized mono-pharmacological inhibitors. Inhibiting LSD1 and UTX, MC3324 induces significant growth arrest and apoptosis in hormone-responsive breast cancer model accompanied by a robust increase in H3K4me2 and H3K27me3. MC3324 down-regulates ERα in breast cancer at both transcriptional and non-transcriptional levels, mimicking the action of a selective endocrine receptor disruptor. MC3324 alters the histone methylation of ERα-regulated promoters, thereby affecting the transcription of genes involved in cell surveillance, hormone response, and death. MC3324 reduces cell proliferation in ex vivo breast cancers, as well as in breast models with acquired resistance to endocrine therapies. Similarly, MC3324 displays tumor-selective potential in vivo, in both xenograft mice and chicken embryo models, with no toxicity and good oral efficacy. This epigenetic multi-target approach is effective and may overcome potential mechanism(s) of resistance in breast cancer.

Hydrogen peroxide (H 2 O 2 ) quantification in biomedicine is valuable as inflammation biomarker but also in assays employing enzymes that generate or consume H 2 O 2 linked to a specific biomarker. Optical H 2 O 2 detection is typically performed through peroxidase-coupled reactions utilizing organic dyes that suffer, however, from poor stability/reproducibility and also cannot be employed in situ in dynamic complex cell cultures to monitor H 2 O 2 levels in real-time. Here, we utilize enzyme-mimetic CeO 2 nanocrystals that are sensitive to H 2 O 2 and study the effect of H 2 O 2 presence on their electronic and luminescent properties. We produce and dope with Eu 3+ these particles in a single-step by flame synthesis and directly deposit them on Si and glass substrates to fabricate nanoparticle layers to monitor in real-time and in situ the H 2 O 2 concentrations generated by Streptococcus pneumoniae clinical isolates. Furthermore, the small CeO 2 :Eu 3+ nanocrystals are combined in a single-step with larger, non-responsive Y 2 O 3 :Tb 3+ nanoparticles during their double-nozzle flame synthesis to engineer hybrid luminescent nanoaggregates as ratiometric robust biosensors. We demonstrate the functionality of these biosensors by monitoring their response in the presence of a broad range of H 2 O 2 concentrations in vitro from S. pneumoniae, highlighting their potential for facile real-time H 2 O 2 detection in vitro in cell cultures., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Microglia have a pivotal role in the pathophysiology of bacterial meningitis. The goal of this review is to provide an overview on how microglia respond to bacterial pathogens targeting the brain, how the interplay between microglia and bacteria can be studied experimentally, and possible ways to use gained knowledge to identify novel preventive and therapeutic strategies. We discuss the dual role of microglia in disease development, the beneficial functions crucial for bacterial clearing, and the destructive properties through triggering neuroinflammation, characterized by cytokine and chemokine release which leads to leukocyte trafficking through the brain vascular endothelium and breakdown of the blood-brain barrier integrity. Due to intrinsic complexity of microglia and up until recently lack of specific markers, the study of microglial response to bacterial pathogens is challenging. New experimental models and techniques open up possibilities to accelerate progress in the field. We review existing models and discuss possibilities and limitations. Finally, we summarize recent findings where bacterial virulence factors are identified to be important for the microglial response, and how manipulation of evoked responses could be used for therapeutic or preventive purposes. Among promising approaches are: modulations of microglia phenotype switching toward anti-inflammatory and phagocytic functions, the use of non-bacterolytic antimicrobials, preventing release of bacterial components into the neural milieu and consequential amplification of immune activation, and protection of the blood-brain barrier integrity.

Immunofluorescent staining using antibodies to detect specific proteins allows for visualization of proteins of interest in a biological sample. In recent years, there have been important advances in the microscopy equipment used for imaging, and we can now perform so-called high-resolution microscopy. Through high-resolution microscopy we can not only study biological processes but also visualize them.

Imaging through the IVIS Spectrum CT system does not provide the resolution at cellular level like the high-resolution or super-resolution microscopy. Rather, it detects bacterial infections in specific anatomical compartments/organs of the animals. The IVIS Spectrum imaging system is a unique imaging technology that allows for real-time monitoring of disease progression in living animals through the use of either bioluminescent or fluorescent probes.

In vivo imaging, meaning imaging tissues in living animals, is still a developing technique. However, microscopy imaging ex vivo remains a very important tool that allows for visualization of biological and pathological processes occurring in vivo. As described in Chap. 5, imaging of animal and human tissue postmortem can be performed at high resolution. Recently, imaging of human tissues infected with pneumococci using an even higher resolution, the so-called super-resolution with STED, has been reported.

Animal models are fundamental tools to study the biology of physiological processes and disease pathogenesis. To study invasive pneumococcal disease (IPD), many models using mice in particular have been established and developed during recent years. Thanks to the advances of the research in the pneumococcal field, nowadays, there is the possibility to use defined mouse models to study each disease caused by the pneumococcus. In this chapter mouse models for pneumonia, bacteremia, and meningitis are described. Since pneumococci are commensal pathogens found to a high extent in healthy individuals. Hence, we also describe a mouse model for nasopharyngeal colonization.

Background: We aimed to assess whether the use of the harmonic scalpel (HS) in axillary dissection would reduce long-term shoulder-arm morbidity compared to traditional instruments (TIs)., Materials and Methods: A retrospective analysis on 180 patients who underwent standard axillary dissection for breast cancer between 2007 and 2015 was carried out. All patients were evaluated for postoperative pain, impairment of shoulder-arm mobility, seroma formation in axilla, frozen shoulder, and lymphedema., Results: HS procedure on average was 50% shorter compared to the TI technique. HS reduced by 4.5 times the risk of axillary seroma. TIs were associated with 4 times higher risk of developing a painful frozen shoulder., Conclusions: Use of the HS was associated with reduced costs and a positive long-term effect on shoulder-arm morbidity. Axillary seromas are not the only reason of later postoperative shoulder-arm morbidity: other mechanisms are hypothesized in the onset of this very disabling disorder., (Copyright © 2018 Elsevier Inc. All rights reserved.)

For the management of Staphylococci coagulase-negative infection, often related to biofilm formation, rapid and accurate identification is necessary in choosing a correct antibiotic therapy. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) is becoming increasingly important for bacterial identification over traditional methods. Our aim was to validate the use of MALDI to discriminate Staphylococcus epidermidis biofilm-producing strains. Clinical strains coming from suture wires were identified and their protein profiles were compared to that obtained from two ATCC reference strains (biofilm producer and non-producer). MALDI identified the eighteen isolates as S. epidermidis , combining sixteen profiles with the biofilm producer and two with the non-producer, confirming the results of crystal violet assay. Our data highlight that MALDI can be considered a good tool to discriminate between biofilm-producer and non-producer strains of S. epidermidis , thus helping to establish an effective antibiotic therapy.

Background: Pneumococci are the major cause of bacterial meningitis globally. To cause meningitis pneumococci interact with the 2 endothelial receptors, polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1), to penetrate the blood-brain barrier (BBB) and invade the brain., Methods: C57BL/6 mice were infected intravenously with bioluminescent pneumococci, and treated with ceftriaxone (1 hour postinfection) and anti-pIgR and PECAM-1 antibodies (1 or 5 hours postinfection), then monitored for 5 and 10 days. Bacterial brain invasion was analyzed using IVIS imaging and bacterial counts., Results: Ceftriaxone, given early after pneumococcal challenge, cleared pneumococci from the blood but not from the brain. After combining ceftriaxone with receptor blockade, using anti-pIgR and PECAM-1 antibodies, we found 100% survival after 5 and 10 days of infection, in contrast to 60% for ceftriaxone alone. Combined antibiotic and antibody treatment resulted in no or few viable bacteria in the brain and no microglia activation. Antibodies remained bound to the receptors during the study period. Receptor blockade did not interfere with antibiotic permeability through the BBB., Conclusions: We suggest that adjunct treatment with pIgR and PECAM-1 antibodies to antibiotics may prevent pneumococcal meningitis development and associated brain damages. However, further evaluations are required.