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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.