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Varicose veins are associated with conditions that impair venous return, such as pregnancy, physical inactivity, valve failure and post-thrombotic syndrome. We report the case of a 50-year-old female patient with history of intermittent calf pain, worsening with prolonged standing posture. She had no previous medical history of either lower extremity trauma or infection. Physical examination showed medial pretibial soft tissue swelling. CT and MRI showed images suggestive of anomalous intraosseous venous drainage with associated bone edema and periosteal reaction. Knowledge of this rare entity is fundamental for proper patient management.

ABSTRACT: Objectives: We report the use of IV dalbavancin in Canadian patients using data captured by the national CLEAR registry. Methods: The CLEAR registry uses the web-based data management program, REDCap™ (online survey https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=TPMWJX98HL) to facilitate clinicians entering details associated with their clinical experiences using IV dalbavancin. Results: Data were available for 40 patients. The most common infections treated were acute bacterial skin and skin structure infection (ABSSSI) (62.5% of patients), bone/joint infection (22.5%), bloodstream/vascular infection (7.5%) and endocarditis (5.0%). Dalbavancin was used as directed (75.0%) and empiric therapy (25.0%). MRSA was the most common identified pathogen (70.0%). Dalbavancin was used both in outpatient (e.g., emergency department) (65.0%), and inpatient treatment settings (e.g., hospital ward) (35.0%). Dalbavancin was used due to the convenience of a single dose treatment (77.5%) as well as to facilitate hospital discharge (7.5%). Dalbavancin was primarily used alone (90.0%), and most commonly using a single 1500 mg dose (77.5%). Microbiological success (pathogen eradicated or presumed eradicated) occurred in 88.2% of known cases, while clinical success (cure and/or improvement) occurred in 93.3% of known cases. No adverse events were reported. Conclusions: In Canada, IV dalbavancin is used as both directed and empiric therapy to treat ABSSSI as well as off-label (bone/joint, bacteremia/vascular, endocarditis, device-related) infections. It is used in both outpatient and inpatient settings due primarily to its convenience as a single-dose treatment regimen and to facilitate early hospital discharge. Dalbavancin use is associated with high microbiological and clinical cure rates along with an excellent safety profile.

A multispecialty trauma team must provide care for pelvic gunshot wounds (PGW) due to the high risk of associated morbidity and mortality, the high density of organs that might be wounded within the pelvis, and the potential consequences of these complicated injuries. We present a case of a 59-year-old woman hemodynamically stable with firearm injury to the left buttock. CT examination showed free air in the peritoneal cavity and in the retroperitoneum and a focal contrast extravasation within the uterine fundus. The patient underwent urgent laparotomy that revealed triple bowel perforation (sigmoid colon, medium rectum, ileum) and a laceration of the posterior and anterior uterine wall at level of the cervix with no signs of active bleeding. The bullet was lodged above the peritoneal reflection, in the right pelvis, and it was removed, and handed over to the judicial authority. The perforated bowel segments were resected with Hartmann's procedure and ileal anastomosis. The uterine laceration was repaired. Although all the viscera and the structures along the trajectory can be harmed, pelvic gunshot wounds have the potential to inflict serious injury. Nongravid uterine traumas are a unique occurrence, and proper care requires an understanding of lesion grading. Finding the gynecological lesion in female patients is essential to receiving the best care and protecting the reproductive system.

The potential of precision population health lies in its capacity to utilize robust patient data for customized prevention and care targeted at specific groups. Machine learning has the potential to automatically identify clinically relevant subgroups of individuals, considering heterogeneous data sources. This study aimed to assess whether unsupervised machine learning (UML) techniques could interpret different clinical data to uncover clinically significant subgroups of patients suspected of coronary artery disease and identify different ranges of aorta dimensions in the different identified subgroups. We employed a random forest-based cluster analysis, utilizing 14 variables from 1170 (717 men/453 women) participants. The unsupervised clustering approach successfully identified four distinct subgroups of individuals with specific clinical characteristics, and this allows us to interpret and assess different ranges of aorta dimensions for each cluster. By employing flexible UML algorithms, we can effectively process heterogeneous patient data and gain deeper insights into clinical interpretation and risk assessment.

Because the deformation parameters (temperature, strain rate) in the actual manufacturing process are non-constant. We investigate meta-dynamic recrystallization behavior under the transient mutation state. First, based on a single-pass thermal deformation experiment and electron backscatter diffraction (EBSD) technique, this study establishes a quantitative calculation method for the volume fraction of meta-dynamic recrystallization under different deformation conditions, and find the GOS threshold basis for judging the occurrence of meta-dynamic recrystallization. Comparing the experimental results with the numerical simulation results, it is found that the MDRX behavior of the material could be accurately described. The meta-dynamic recrystallization evolution law of the material in the thermal deformation insulation stage under the variable strain rate state is investigated by continuous variable rate thermal deformation experiment and numerical simulation. It is observed that an increase of the average strain rate in the continuous variable strain rate state would promote the meta-dynamic recrystallization softening behavior of the material in comparison with the steady state deformation stage, and vice versa.

Small bowel jejunoileal diverticulosis is an uncommon and usually asymptomatic condition. Complications may occur such as acute diverticulitis including infection or perforation, bleeding, small bowel obstruction and volvulus. Herein we report a case of a 76 years-old woman with acute left side abdominal pain and tenderness. A clinical suspected diagnosis of colonic diverticulitis was formulated. She underwent Ultrasound that revealed a collapsed small bowel loop with a large sac-like out-pouching lesion with mixed content (fluid and pockets of air) associated to hyperechogenicity of perilesional fat. Because of the atypical US findings, the patient underwent abdominopelvic CT that confirmed that the large sac-like out-pouching was a jejunal inflamed diverticulum. The patient underwent emergency surgery. Radiologist should be aware of imaging findings of jejunoileal diverticulitis in order to achieve a prompt diagnosis.

Objective: Left atrial appendage closure (LAAC) concomitant to heart surgery in patients with underlying atrial fibrillation (AF) has gained attention because of long-term reduction of thromboembolic complications. As of mortality benefits in the setting of non-AF, data from both observational studies and randomized controlled trials are conflicting. Methods: On-line databases were screened for studies comparing LAAC versus no LAAC concomitant to other heart surgery. End points assessed were all-cause mortality and stroke at early and longest-available follow-up. Subgroup analyses stratified on preoperative AF were performed. Risk ratios (RR) with 95% CIs served as primary statistics. Results: Electronic search yielded 25 studies (N = 660 [158 patients]). There was no difference between LAAC and no LAAC in terms of early mortality. In the overall population analysis, LAAC reduced long-term mortality (RR, 0.86; 95% CI, 0.74-1.00; P = .05; I2 = 88%), reduced early stroke risk by 19% (RR, 0.81; 95% CI, 0.72-0.93; P = .002; I2 = 57%), and reduced late stroke risk by 13% (RR, 0.87; 95% CI, 0.84-0.90; P

Daylight is essential for ecosystems and for the physical and mental well-being of people. In densely populated cities, only a small proportion of total daylight is available to support urban greenery and most people have little daily exposure to natural daylight. Despite this, many cities have followed a strategy of densification as a way of preventing urban sprawl and reducing energy consumption. In this article, we review the biological importance of daylight and show that urban densification leads to a reduction in the daylight available for both people and nature. We conclude that daylight in cities should be treated as a limiting resource that needs to be planned and managed carefully, much like water or energy. We suggest elements for a policy framework aimed at optimizing urban daylight, including how to determine daylight needs, how to determine the maximum viable urban density, and policy options for built and unbuilt areas.

ABSTRACT: Objectives: The main aim of this study was to evaluate the antibiofilm activity of cefiderocol alone and in combination with imipenem vs. sessile cells of Pseudomonas aeruginosa, assessing a potential synergistic bactericidal effect. Methods: Ten P. aeruginosa clinical isolates from infected implants and bloodstream were included in the study. Cefiderocol was tested alone and in combination with imipenem on 24-h-old P. aeruginosa biofilm formed on porous glass beads. For each antibiotic formulation, minimum bactericidal biofilm concentration (MBBC), defined as the lowest concentration that determined a reduction of at least 3 log10 CFU/mL compared with the untreated control, was evaluated. Scanning electron microscopy (SEM) was used to investigate the biofilm of P. aeruginosa treated with cefiderocol, imipenem, or their combination. Results: Cefiderocol and imipenem were tested alone on P. aeruginosa biofilm and a reasonable reduction in the number of viable cells was observed, especially at high drug concentrations tested. The synergistic effect of cefiderocol in combination with imipenem was evaluated for five selected isolates. Cotreatment with the two drugs led to a remarkable reduction of cell viability by resulting in synergistic bactericidal activity in all tested strains and in synergistic eradicating activity in only one isolate. SEM analysis revealed that, in cefiderocol-treated biofilm, bacterial cells became more elongated than in the untreated control, forming filaments in which bacterial division seems to be inhibited. Conclusions: Cefiderocol exhibited an encouraging antibiofilm activity against tested strains, representing a valid option for the treatment of P. aeruginosa biofilm-associated infections, especially when administered in combination with imipenem.

Background: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening. Methods: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP). Results: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users. Among RV254 participants, reactivity in Ag/Ab assays was

The fragmented design of intelligent transportation systems creates isolated intelligent systems. Resource competition and information gaps are fierce and widespread, worsening traffic issues and degrading overall service levels. Therefore, empowered by advanced technologies, an evolution toward an autonomous transportation system (ATS) is observed. This evolution aims to develop a collaborative and sustainable ecosystem, prompting interoperability within the cloud-edge-device continuum. It can, accordingly, dismantle internal resource barriers and achieve a systematic balance between demand and supply with less human intervention. Despite the promising vision of an ATS, it encounters three key challenges: disparate data, deficient models, and conflicting interests in supporting autonomous and personalized mobility. Hence, as an innovative solution, a trustworthy, private, and equal-serving framework called TPE is designed. It seamlessly integrates blockchain, federated learning, and large-scale models to deploy a trustworthy operating environment, process private data for globally shareable knowledge, and develop a foundation model for personalized adaptation, respectively. Consequently, ATSs empowered by TPE can serve diverse user groups both privately and equally.

Background: Seasonal allergic rhinoconjunctivitis (SAR) is a worldwide health problem, especially in Westernized countries. Previous studies of the “Panallergens in Pediatrics” (PAN-PED) cohort found that molecular spreading (ie, the progressive increase in serum specific IgE antibody levels) of the IgE response to the grass pollen, Phleum pratense, molecules is directly associated with polysensitization to pollen in general.The research question is aimed at verifying whether this association can also be detected for non-pollen allergens, specifically Dermatophagoides pteronyssinnus (D.pt), to better understand the relationship between a perennial allergen (D.pt) and a seasonal allergen (Phleum pratense).To this end, our first objective was to analyze the biobank of the PAN-PED cohort serum by measuring the IgE levels to D.pt and its major recombinant molecules (Der p1, Der p2, Der p23); subsequently we investigated their correlation towards Phleum pratense IgE response, studying also the relationship between the molecular spreading of these 2 different allergens. Methods: Among 1120 patients positive to Phleum pratense, 638 were also sensitized to D.pt. Patients underwent skin prick tests (SPT) for inhalant extracts, and their serum was tested for total IgE (tIgE), and sIgE to pollen and perennial allergens. Considering the molecular allergen detection through the component resolved diagnosis (CRD), out of 638 patients, 146 were further investigated by performing IgE tests of the 3 major D.pt. molecules: Der p1, Der p2, and Der p23. Results: We found that a broader molecular response to Phleum pratense molecules, assessed by CRD, was associated with higher tIgE levels, polysensitization to pollens, and higher IgE levels to pollens, but also to lower IgE levels to D.pt and lower degree of sensitization to rDer p1, r Der p2, and rDer p23. In a multivariate linear model, the number of Phleum pratense molecules recognized by IgE was still inversely associated with the IgE level to D.pt extract. Conclusions: The main finding of this study was the detection of an inverse association, never described in the literature, between the molecular spreading of the IgE response to Phleum pratense and the IgE response to D.pt. This led us to speculate on the etiopathogenetic hypothesis according to which, among the majority of pollen allergic patients, a strong and molecularly diversified IgE response may be limited to pollen allergens and may be preventing or contrasting the development of an equally strong and diversified IgE sensitization to D.pt molecules. The biological mechanisms underlying this phenomenon deserve to be investigated.

Eosinophilic esophagitis (EoE) and allergic rhinitis (AR) usually represent the latest manifestations of the atopic march, sharing a common type 2 inflammation response. A relevant prevalence of AR in EoE cohorts has been widely confirmed. An increasing literature assessed the involvement of aeroantigens in EoE pathogenesis, focusing foremost on the seasonality of new diagnoses, symptoms, and response to therapy. Unfortunately, no diriment direction has been achieved, probably due to the retrospective design of the studies so far available, which chose surrogate markers of EoE activity (mostly the date of new diagnosis) which may be affected by geographical, logistic and personal factors, probably not dependent by the disease itself. EoE exacerbations reported in the context of the pollen levels (preferably pollen counts) may represent a more reliable marker. AR might promote the onset and the re-exacerbation of EoE through mechanisms that are both local (ie, massive exposure to airborne antigens mediated by post-nasal drip) and systemic (type 2 inflammation). Furthermore, AR may facilitate EoE onset by predisposing to pollen food allergic syndrome (PFAS), and EoE patients with PFAS reported higher rate of AR, thus suggesting a bond among these 3 conditions whose causative relationship have still to be ascertained. In addition, because of its shifting activity from Th2 to Th1 inflammation, several case reports focused on the effect of allergen immunotherapy (AIT) employed to treat AR in EoE patients. Also in this instance, no certainties could be guaranteed, although sublingual immunotherapy (SLIT) is more frequently reported to exacerbate EoE, while SCIT is mostly described as a remission adjuvant. The real life experience reported from our allergy service appears to confirm such hypothesis. Finally, a watchful eye should be reserved to monoclonal antibodies as a potential future option for concomitant EoE and AR. In light of all this, an attentive evaluation of allergic history of EoE patients should be relevant. Future perspectives should be addressed on prospective studies targeted to shed light on causative relations among airborne antigens, AR and EoE, and to viable comprehensive treatments.

Background: Serodiagnosis of TORCH infections should be performed in pre-pregnancy and reproductive-age women to prevent vertical transmission. Herein, we conducted a 5-year cross-sectional retrospective study in childbearing age women to provide prevalence data. Also, stratifying the cohort into three age groups, we identified those most susceptible to acute TORCH infections. Methods: Between 2019 and 2023, serum samples from 2286 childbearing age women attending the “R. Dulbecco” University Hospital of Catanzaro were collected. Screening for TORCH pathogens, such as: Toxoplasma gondii (TOX), Cytomegalovirus (CMV), Rubella Virus (RUB), Parvovirus B19 (ParvoB19), Herpes Simplex Virus types 1 and 2 (HSV1, HSV2) and Treponema pallidum was carried out using serological tests. Chemiluminescent immunoassay was performed to detect TOX, CMV and ParvoB19 Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies, while Enzyme Linked Fluorescent Assay was performed to detect RUB IgM and IgG antibodies and CMV and TOX IgG Avidity. Enzyme Linked Immunosorbent Assay was performed to detect HSV1 IgG, HSV2 IgG, HSV1/2 IgM, T. pallidum total antibodies and RUB IgG Avidity. Binomial logistic regression models were developed to compare seroprevalence rates among different age groups. Results: The highest immunological protection was observed for RUB infection (87 %), probably associated with vaccination practice, followed by HSV1 and CMV (82 % and 63 %). The 16–25 year age group results as the most susceptible to acute infections as demonstrated by odds of CMV IgM positivity (primary infection) which decreased with age. Conclusions: The TORCH serological screening program should be implemented in women before pregnancy to formulate strategies for serological screening of childbearing age women and guiding clinicians in making decisions.

Soil nematodes are among the most significant soil-dwelling organisms in forest ecosystems. However, the factors that shape the distribution of soil nematodes are still not well explored. Therefore, we collected soil samples from 20 forest sites along the eastern transect of China and sequenced 18S rRNA V9 region to reveal the biodiversity of soil nematodes. Our study found that soil nematode richness is higher in temperate mixed needleleaf and broadleaf forests compared with the other four vegetation regions. Soil physiochemical properties overrode climatic factors to be the primary drivers of soil nematode richness and community composition. Importantly, the soil nematode richness significantly enhanced ecosystem multifunctionality, especially bacterial biomass and enzyme activities, with a determination coefficient (r2) of 0.23, suggesting that soil nematodes played essential roles in the forest ecosystem.

This paper examined the relationship among countermovement jump (CMJ), football category, chronological age, relative age, and pubertal development status to investigate which parameter could be better associated with jumping performance. We tested 259 young male football players (14.9 ± 1.8 yrs; 169.7 ± 9.8 cm; 60.6 ± 11.3 kg; 20.9 ± 2.6 kg m−2) belonging to elite football academies. One-sample chi-square tests were used to test the uniformity of distributions of the proportions of players in each year quarter (relative age effect, RAE) for the whole sample and stratified for each football age category (U14, U15, U17, and U19). One-way ANOVAs were used to test the associations among a) categories, RAE, and CMJ, and b) the pubertal status category and CMJ. Pearson's correlation assessed the relationship among variables. The birth distribution among the year's quarters significantly differed from the expected proportion of 25 % of participants each quarter (χ2 = 41.74; p

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension. Liver biopsy is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyltransferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. Methods: The study included all patients who underwent liver biopsy for persistent and unexplained GGT elevation in five Italian hepatology units between March 2015 and December 2021. Results: A total of 144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only 12 (8.3%) had liver stiffness measurements (LSM) >10 kPa, while 7 (4.8%) had ultrasound evidence of portal hypertension. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%) patients. Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio [OR] 2.60, 95% CI 1.13-5.99), LSM

Mathur and Mehta won the third prize in the 2023 Gravity Research Foundation Essay Competition for proving the universality of black hole (BH) thermodynamics. Specifically, they demonstrated that any Extremely Compact Object (ECO) must have the same BH thermodynamic properties regardless of whether or not the ECO possesses an event horizon. The result is remarkable, but it was obtained under the approximation according to which the BH emission spectrum has an exactly thermal character. In fact, strong arguments based on energy conservation and BH back reaction imply that the spectrum of the Hawking radiation cannot be exactly thermal. In this work the result of Mathur and Mehta will be extended to the case where the radiation spectrum is not exactly thermal using the concept of BH dynamical state.

Casein kinase II (CK2) has recently emerged as a pivotal mediator in the propagation of inflammation across various diseases. Nevertheless, its role in the pathogenesis of sepsis remains unexplored. Here, we investigated the involvement of CK2 in sepsis progression and the potential beneficial effects of silmitasertib, a selective and potent CK2α inhibitor, currently under clinical trials for COVID-19 and cancer. Sepsis was induced by caecal ligation and puncture (CLP) in four-month-old C57BL/6OlaHsd mice. One hour after the CLP/Sham procedure, animals were assigned to receive silmitasertib (50 mg/kg/i.v.) or vehicle. Plasma/organs were collected at 24 h for analysis. A second set of experiments was performed for survival rate over 120 h. Septic mice developed multiorgan failure, including renal dysfunction due to hypoperfusion (reduced renal blood flow) and increased plasma levels of creatinine. Renal derangements were associated with local overactivation of CK2, and downstream activation of the NF-ĸB-iNOS-NO axis, paralleled by a systemic cytokine storm. Interestingly, all markers of injury/inflammation were mitigated following silmitasertib administration. Additionally, when compared to sham-operated mice, sepsis led to vascular hyporesponsiveness due to an aberrant systemic and local release of NO. Silmitasertib restored sepsis-induced vascular abnormalities. Overall, these pharmacological effects of silmitasertib significantly reduced sepsis mortality. Our findings reveal, for the first time, the potential benefits of a selective and potent CK2 inhibitor to counteract sepsis-induced hyperinflammatory storm, vasoplegia, and ultimately prolonging the survival of septic mice, thus suggesting a pivotal role of CK2 in sepsis and silmitasertib as a novel powerful pharmacological tool for drug repurposing in sepsis.

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Objectives: To retrospectively describe the patterns of use of dalbavancin for treating infections in diabetic patients in Italian and Spanish standard clinical practice. Methods: DALBADIA [NCT04959799] was a multicentre, observational, retrospective cohort study, conducted in Italy and Spain. The study enrolled 97 adults with type 1 or 2 diabetes mellitus, treated with dalbavancin as per standard clinical practice for a Gram-positive bacterial infection or the Gram-positive component of a mixed infection. Results: Dalbavancin was used to treat cellulitis (18/92 patients, 19.6%), followed by prosthetic joint infection (14 patients, 15.2%), endocarditis (13 patients, 14.1%), and primary bacteraemia (10 patients, 10.9%); 78/92 (84.8%) patients had Gram-positive infections only, and 14 (15.2%) had mixed infections. The most frequently isolated microorganisms were Staphylococcus aureus in 43 (55.8% of the patients with microbial isolation), 25.6% of which methicillin-resistant; Staphylococcus epidermidis in 13 (16.9%), 53.8% of which methicillin-resistant; Enterococcus faecalis in 11 (14.3%). The main reason for the dalbavancin choice was the intent to simplify the antibiotic regimen (81.5% of cases). A multidisciplinary team participated in the treatment choice process for 53 (57.6%) patients. Dalbavancin was given as first-line antibiotic in 34 (37.0%) patients and administered as one infusion in 32 (34.8%), and as two infusions in 39 (42.4%). In total, 57/62 (91.9%) eligible patients with available assessment were judged clinically cured or improved at the end of observation. Conclusion: In clinical practice, dalbavancin was used in diabetic patients to treat ABSSSIs and other difficult-to-treat infections with a favourable safety profile and a high rate of positive clinical responses.

Objectives: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy. Methods: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves. Results: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age

Background and aims: Cardiac ParaGangliomas (PGLs) are rare extra-adrenal tumours that arise from chromaffin cells of the sympathetic ganglia. PGL are often diagnosed incidentally, with no symptoms or symptoms related to cardiovascular dysfunction. Methods: Cardiac Computed Tomography (CCT) and Cardiac Magnetic Resonance (CMR) can detect the correct morphology and position of the lesion and provide proper tissue characterization.Nuclear medicine imaging, with Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) with specific radiotracers, can evaluate the functionality of the PGL and to distinguish a secreting from a non-secreting tumour. Results: In association with biochemical parameters, a multimodal imaging approach, not yet standardized, can be useful both in the diagnosis, in the monitoring and in the treatment planning. Conclusions: In this systematic review, we aim to investigate the role of diagnostic imaging, in particular CCT, CMR, PET and SPECT in diagnosis, characterization and monitoring of cardiac PGLs.

Gill health is crucial for maintaining respiratory and immunological functions in fish, yet it is often compromised by parasitic infections and treatments. This study investigates the effects of amoebic gill disease (AGD) and peracetic acid (PAA) treatment on mucous cell (MC) parameters in the gill filaments of Atlantic salmon (Salmo salar). Although exposure to AGD, with or without PAA treatment, did not cause changes in the mucosal parameters of the skin in Atlantic salmon, there was an increase in the mucosal parameters in the gill filaments 24 h post-treatment and a significant increase four weeks post-treatment. These findings suggest that while AGD and PAA treatment do not affect skin mucosa, they disrupt mucosal homeostasis in the gill filaments as well as in the gill lamellae. In AGD-affected fish, hyperplasia and hypertrophy of MCs in both gill lamellae and filaments increase the diffusion distance across the water-blood barrier, leading to respiratory disturbances.

Objective: To present the surgical technique and outcomes of robotic ureteral reimplantation in ileal conduit (IC) and neobladder (NB) in patients with prior minimally-invasive radical cystectomy and intracorporeal urinary diversion, who developed benign uretero-ileal anastomotic strictures. Patients and surgical procedure: We report on a multiinstitutional cohort of 10 patients (7 IC, 3 NB) who had 12 uretero-ileal strictures (8 unilateral, 2 bilateral) causing hydronephrosis and renal function deterioration, who underwent robotic uretero-ileal reimplantation in referral centers for robotic surgery between 2016 and 2022. Median age was 67.5 years (Interquartile range [IQR]: 66–69). The stricture was diagnosed at a median of 6 months (IQR 5–10) from the initial surgery. All unilateral strictures were on the left side. Two patients received unsuccessful endoscopic dilatation before the reconstructive surgery. All patients underwent nephrostomy placement prior to the reconstructive procedure. Robotic uretero-ileal reanastomosis started with adhesiolysis, followed by the identification of the ureters and urinary diversion, facilitated by the use of intracavitary saline or ICG. When dissecting the ureters, a „no touch” technique was used, in order to minimize devascularization and ischemia. Localization of the ureteral stricture was critical. The excision of the entire ischemic segment was performed until signs indicative of adequate tissue trophism were found. At the same time, consideration was given to spare sufficient length of the ureteral stumps to allow for a tension-free anastomosis. Direct anastomosis using monofilament resorbable suture, with insertion of mono J or double J stent was performed with both ileal conduit and neobladder. Bricker technique was used in case of unilateral stricture. Results: The median operative time for robotic uretero-ileal reanastomosis was 152 min (IQR 120–180) and the median blood loss was 50 ml (IQR 40–70). No intraoperative complications occurred according to the ICARUS criteria. Median length of hospital stay was 4.5 days (IQR 3–6). Two Clavien-DIndo II (20 %) postoperative complications were registered (urinary tract infection and acute kidney injury). No patients required readmission or reoperation. The mean length of ureteral catheterization for reimplantation in IC was 20.7 days (± 4.29). For patients with NB, the mean ureteral and urethral catheterization times were 54.3 days (± 22.8) and 19.3 days (± 11.08), respectively. The ureteral stents were removed in all patients. At a median of 16 months follow-up (range 6–36 months), 2 patients (one IC and one NB, respectively) had persistent hydronephrosis. Conclusion: In patients requiring surgery for benign ureteral strictures following cystectomy, robotic surgery allows for safe and efficient ureteral reimplantation in urinary diversion.

Objective: The purpose of this study was to investigate how parents of children with complex care needs conceptualize burnout from the perspective of parents themselves. Methods: We conducted semi-structured interviews with 38 parents, selected for maximal variation in parental, child, and family characteristics. Inductive thematic analysis was employed. Results: Burnout was conceptualized as encompassing three themes: having a reoccurring long-term nature, commencing with symptoms of stress progressing into exhaustion, and ending in a survival mode wherein parents worked hard to project an image of everything being well and under control (fighting) while distancing physically and emotionally from others and themselves (fleeing). Conclusion: Burnout involves specific aspects of caregiving and parenting, such as long-term responsibility for the child, which cannot be relinquished. Furthermore, burnout may also be ‘hidden’: not always showing to the outside world, which requires extra attention and vigilance among parent's informal and formal networks. Awareness of the various interpretations of the term may foster constructive communication. Innovation: Focusing on parents’ individual experiences has illuminated new aspects of burnout. By purposively sampling a variety of parents of children with complex care needs, a broader understanding of the meaning of the term ‘burnout’ from the perspective of parents was achieved.

Background: Visceral Leishmaniasis is a neglected tropical disease with a high rate of infection and mortality in affected areas. Around 50,000 to 90,000 new cases of visceral leishmaniasis (VL) are estimated every year. Individuals asymptomatic for the disease should also be considered in epidemiological surveillance of the disease, as they can help spread the parasite. Thus, the development of low-cost diagnosis methods that allow the identification of infected and asymptomatic individuals is required, especially in developing countries where this disease is endemic. Results: In this work, we developed an immunosensor for recognizing anti-Leishmania antibodies in asymptomatic individuals and avoiding cross-reaction with Chagas disease (CD). For that, we used carbon-based screen-printed electrodes, modified with graphene oxide and gold. Reproducibility was assessed by calculating the relative standard deviation (RSD < 5 %) from cyclic voltammograms of [Fe(CN)6]3-/4− using three different electrodes, screen-printed carbon electrodes (DPR-110) and graphene modified screen-printed electrodes (DPR-110 GPH) were purchased from DropSens (Oviedo, Asturias, Spain). Significance: As an electrochemical methodology, we use cyclic voltammetry. After the tests were carried out, we considered that carbon electrodes adsorbed with reduced graphene oxide and modified with gold nanoparticles were the best platforms for detecting anti-Leishmania antibodies. In the study carried out, the limit of quantification (LOQ) for anti-Leishmania antibodies was established at 16.75 mg/mL, while the limit of detection (LOD) was 5.58 mg/mL. These limits indicate the minimum antibody concentration values that can be quantified and detected accurately and reliably in the analyzed sera.

Context: The occurrence of upper urinary tract urothelial carcinoma (UTUC) is uncommon and is usually identified at an advanced and multifocal stage. Currently, there is growing interest in utilizing endoscopic laser ablation (ELA). Objective: To evaluate the survival rates and perioperative complications of ELA. Evidence acquisition: We performed a literature search through PubMed, Web of Science, and Scopus. The analysis included observational studies that examined the oncological outcomes of patients with UTUC treated with ELA. Evidence synthesis: Neodymium and diode lasers are no longer used due to their high complication rates. Holmium:yttrium-aluminum-garnet (YAG) and thulium:YAG lasers provided excellent tumor ablation and hemostasis in both the collecting system and the ureter. These lasers offer good disease-free and cancer-specific survival, especially for low-grade tumors. Conclusions: Advancements in laser technology and ablation techniques, and understanding of UTUC tumor biology hold significant promise in improving the use of conservative UTUC treatment, with excellent safety and good oncological outcomes for low-grade diseases. Patient summary: With the advancement of technology, the conservative approach utilizing endoscopic laser ablation for upper tract urothelial tumors has been proved to be both safe and effective, showcasing promising survival rates.

Summary: Developing active and stable catalysts for carbon-free hydrogen production is crucial to mitigate the effects of climate change. Ammonia is a promising carbon-free hydrogen source, as it has a high hydrogen content and is liquid at low pressure, which allows its easy storage and transportation. We have recently developed a nickel-based catalyst with a small content of ruthenium supported on cerium oxide, which exhibits high activity and stability in ammonia decomposition. Here, we investigate mechanochemical milling for its synthesis, a faster and less energy-consuming technique than conventional ones. Results indicate that mechanochemical synthesis increases catalytic activity compared to the conventional incipient wetness impregnation method. The interaction between the metal precursors and the support is key in fine-tuning catalytic activity, which increases linearly with oxygen vacancies in the support. Moreover, the mechanochemical method modifies the oxidation state of Ni and Ru species, with a variation depending on the precursors.

Purpose: To analyze the presenting symptoms and clinical examination findings of patients undergoing meniscal root repairs to aid physicians in diagnosing this injury. Methods: All patients undergoing isolated arthroscopic meniscal root repair from January 1, 2016, to September 1, 2021, were identified. Patients younger than the age of 40 years were excluded. Clinical notes were reviewed for presenting symptoms and physical examination findings. Preoperative radiographs were graded using the Kellgren-Lawrence (KL) scale for osteoarthritis. Root tears were graded using the radiographic criteria of Chung et al. and articular cartilage injury was graded using a validated system, AMADEUS (mean total Area Measurement And Depth & Underlying Structures). Results: In total, 221 patients met inclusion criteria; 65.6% of patients reported that their pain began after an acute injury, with 39.4% of patients reporting a “pop.” On examination, an effusion was present in 71% of knees. McMurray test was reported positive in 85.5% and a positive hyperflexion test in 53.8% of knees. In total, 49.5% of knees were graded KL 1. 154 had medial root tears, 10 had lateral root tears, and 24 suffered both root tears. In total, 44.1% of tears occurred at the midsubstance of the root, with 28.0% occurring at the enthesis and 28.0% occurring at the root-posterior horn junction. The mean AMADEUS score was 94.4 ± 11.4. Conclusions: Although most patients reported pain began after acute injury, less than one-half reported hearing a “pop.” When patients were evaluated, an effusion, positive McMurray test, and positive hyperflexion test were present in most meniscal root tears. Level of Evidence: Level IV, diagnostic case series.

Purpose: To compare the outcomes of patients undergoing partial meniscectomy preoperatively identified with the “meniscal comma sign” with those undergoing meniscectomy with other tear patterns. Methods: Patients with meniscal “comma sign,” as indicated by a query of magnetic resonance imaging reports, were screened using the search terms “meniscotibial recess,” “meniscus perched over the medial tibial margin,” or other search terms by radiologists between January 2008 and November 2019. Patients were matched and chart review was done for demographics, revision surgery, and progression to total knee arthroplasty. Radiographs were used for osteoarthritis grading using the Kellgren-Lawrence (KL) scoring system. Preoperative and postoperative International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Lysholm, and Short Form 12-item Survey scores were collected. Results: A total of 406 patients met inclusion (comma sign = 197; control group = 209). The control group had an increased duration of symptoms at the initial visit (P = .001). More patients with the meniscal comma sign received corticosteroid knee injections before surgery (P = .011), and they also had greater mean KL scores (P = .001) as well as greater KL categorical scores (P = .002), indicating more advanced levels or arthritis. There were no differences in those receiving physical therapy (PT) before surgery (P = .966) or those receiving injections or PT after surgery (P = .631, P = .37, respectively). International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Lysholm, and Short Form 12-Item Survey Physical scores improved preoperatively to postoperatively in both groups (P < .05), and there was no difference between the case and control group (P > .05). No significant difference was found in revisions or progression to total knee arthroplasty between cohorts. (P = .676 and P = .424). Conclusions: Patients presenting with preoperative findings of meniscal comma sign fare similarly to those that do not. Patients with this meniscal injury tend to have more advanced grading of osteoarthritic changes in the knee at presentation and seek care earlier than those without. Arthroscopic meniscectomy is a good treatment option for patients with a meniscal fragment in the meniscotibial recess and shows outcomes comparable with those with other tear patterns. Level of Evidence: Level III, retrospective cohort.

Arteriovenous malformation of the brain (bAVM) is a vascular phenotype related to brain defective angiogenesis. Involved vessels show impaired expression of vascular differentiation markers resulting in the arteriolar to venule direct shunt. In order to clarify aberrant gene expression occurring in bAVM, here we describe results obtained by methylome analysis performed on endothelial cells (ECs) isolated from bAVM specimens, compared to human cerebral microvascular ECs. Results were validated by quantitative methylation-specific PCR and quantitative realtime-PCR. Differential methylation events occur in genes already linked to bAVM onset, as RBPJ and KRAS. However, among differentially methylated genes, we identified EPHB1 and several other loci involved in EC adhesion as well as in EC/vascular smooth muscle cell (VSMC) crosstalk, suggesting that only endothelial dysfunction might not be sufficient to trigger the bAVM phenotype. Moreover, aberrant methylation pattern was reported for many lncRNA genes targeting transcription factors expressed during neurovascular development. Among these, the YBX1 that was recently shown to target the arteridin coding gene. Finally, in addition to the conventional CpG methylation, we further considered the role of impaired CHG methylation, mainly occurring in brain at embryo stage. We showed as differentially CHG methylated genes are clustered in pathways related to EC homeostasis, as well as to VSMC-EC crosstalk, suggesting as impairment of this interaction plays a prominent role in loss of vascular differentiation, in bAVM phenotype.

Asparagine and glutamine depletion operated by the drug Asparaginase (ASNase) has revolutionized therapy in pediatric patients affected by Acute Lymphoblastic Leukemia (ALL), bringing remissions to a remarkable 90 % of cases. However, the knowledge of the proproliferative role of asparagine in adult and solid tumors is still limited. We have here analyzed the effect of ASNase on three adenocarcinoma cell lines (A549, lung adenocarcinoma, MCF-7, breast cancer, and 786-O, kidney cancer). In contrast to MCF-7 cells, 786-O and A549 cells proved to be a relevant target for cell cycle perturbation by asparagine and glutamine shortage. Indeed, when the cell-cycle was analyzed by flow cytometry, A549 showed a canonical response to asparaginase, 786-O cells, instead, showed a reduction of the percentage of cells in the G1 phase and an increase of those in the S-phase. Despite an increased number of PCNA and RPA70 positive nuclear foci, BrdU and EdU incorporation was absent or strongly delayed in treated 786-O cells, thus indicating a readiness of replication forks unmatched by DNA synthesis. In 786-O asparagine synthetase was reduced following treatment and glutamine synthetase was totally absent. Interestingly, DNA synthesis could be recovered by adding Gln to the medium. MCF-7 cells showed no significant changes in the cell cycle phases, in DNA-bound PCNA and in total PCNA, but a significant increase in ASNS and GS mRNA and protein expression. The collected data suggest that the effect observed on 786-O cells following ASNase treatment could rely on mechanisms which differ from those well-known and described for leukemic blasts, consisting of a complete block in the G1/S transition in proliferating cells and on an increase on non-proliferative (G0) blasts.

Green Chemistry involves applying a set of principles aimed at minimizing the use of hazardous substances in the design, production, and application of chemical products. In recent decades, Ionic Liquids (ILs) have emerged as more environmentally friendly substitutes for traditional organic solvents. This preference is primarily due to their low vapor pressure, which results in minimal atmospheric pollution and enhanced industrial safety. However, existing literature highlights the toxicity of ILs towards aquatic invertebrates. Consequently, this study points to assess the biochemical effects of a selection of ILs through an in vitro approach. Specifically, digestive gland and gill cellular fractions (S9) of the marine bivalve Mytilus galloprovincialis were exposed to varying concentrations (0.05–2 μM) of three ILs featuring identical cations but different anions. The ILs tested were 1-ethyl-3-methylimidazolium octanoate ([EMIM][Oct]), 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), and 1-ethyl-3-methylimidazolium ethyl sulfate ([EMIM][EtSO4]). The results indicate that [EMIM][Oct] induces higher toxicity in both S9 tissues, highlighting a strong effect of the anion. Overall, antioxidant and biotransformation defenses were significantly altered for all three ILs assessed. While acetylcholinesterase activity was significantly inhibited of about half of control activity, indicating neurotoxic damage as part of the toxicity mode of action of these ILs, neither lipid peroxidation nor alterations to DNA integrity were observed (≥100 %). This study supports the use of in vitro techniques as important tools capable of generating reliable ecotoxicological data, which can be further considered as a screening before in vivo testing and used for in silico modeling.

Summary: Periventricular nodular heterotopia (PNH), the most common brain malformation diagnosed in adulthood, is characterized by the presence of neuronal nodules along the ventricular walls. PNH is mainly associated with mutations in the FLNA gene – encoding an actin-binding protein - and patients often develop epilepsy. However, the molecular mechanisms underlying the neuronal failure still remain elusive. It has been hypothesized that dysfunctional cortical circuitry, rather than ectopic neurons, may explain the clinical manifestations. To address this issue, we depleted FLNA from cortical pyramidal neurons of a conditional Flnaflox/flox mice by timed in utero electroporation of Cre recombinase. We found that FLNA regulates dendritogenesis and spinogenesis thus promoting an appropriate excitatory/inhibitory inputs balance. We demonstrated that FLNA modulates RAC1 and cofilin activity through its interaction with the Rho-GTPase Activating Protein 24 (ARHGAP24). Collectively, we disclose an uncharacterized role of FLNA and provide strong support for neural circuit dysfunction being a consequence of FLNA mutations.

Summary: Noxious stimuli activate nociceptive sensory neurons, causing action potential firing and the release of diverse signaling molecules. Several peptides have already been identified to be released by sensory neurons and shown to modulate inflammatory responses and inflammatory pain. However, it is still unclear whether lipid mediators can be released upon sensory neuron activation to modulate intercellular communication. Here, we analyzed the lipid secretome of capsaicin-stimulated nociceptive neurons with LC-HRMS, revealing that oleic acid is strongly released from sensory neurons by capsaicin. We further demonstrated that oleic acid inhibits capsaicin-induced calcium transients in sensory neurons and reverses bradykinin-induced TRPV1 sensitization by a calcineurin (CaN) and GPR40 (FFAR1) dependent pathway. Additionally, oleic acid alleviated zymosan-mediated thermal hypersensitivity via the GPR40, suggesting that the capsaicin-mediated oleic acid release from sensory neurons acts as a protective and feedback mechanism, preventing sensory neurons from nociceptive overstimulation via the GPR40/CaN/TRPV1-axis.

Weak posture is a widely recognized problem affecting individuals of all ages, that can lead to back pain, which is a significant socio-economic burden in civil societies. Posture assessment enables the early detection of postural deficiencies, thus enabling proactive interventions. Therefore, it is an important tool for promoting public health, not only in childhood and adolescence. This article provides posture data of 1,149 subjects aged 10 to 69 years measured by stereophotogrammetry. In addition to subject anthropometrics, raw sagittal posture parameters as well as calculated flèche cervicale (FC), flèche lombaire (FL), and kyphosis index (KI) and the respective values normalized to the trunk height (FC%, FL%, KI%) are provided. Further, based on the measurements and a visual inspection, biomedical experts made a classification of the presence of hyperkyphosis of the thoracic spine or hyperlordosis of the lumbar spine. In a second step, these assessments were algorithmically checked for label quality due to possible errors of the raters. Critical cases were reassessed by experts. In addition to the original ratings, these corrected labels are also reported. The data offers potential for data driven objective posture assessment and the development of diagnostic supportive machine learning applications.

Hydrogen sulphide (H2S) is considered an immunotoxicant, and its presence in the water can influence the mucosal barrier functions of fish. However, there is a significant knowledge gap on how fish mucosa responds to low environmental H2S levels. The present study investigated the consequences of prolonged exposure to sub-lethal levels of H2S on the mucosal defences of Atlantic salmon (Salmo salar). Fish were continuously exposed to two levels of H2S (low: 0.05 µM; and high: 0.12 µM) for 12 days. Unexposed fish served as control. Molecular and histological profiling focused on the changes in the skin, gills and olfactory rosette. In addition, metabolomics and proteomics were performed on the skin and gill mucus. The gene expression profile indicated that the gills and olfactory rosette were more sensitive to H2S than the skin. The olfactory rosette showed a dose-dependent response, but not the gills. Genes related to stress responses were triggered at mucosal sites by H2S. Moreover, H2S elicited strong inflammatory responses, particularly in the gills. All mucosal organs demonstrated the key molecular repertoire for sulphide detoxification, but their temporal and spatial expression was not substantially affected by sub-lethal H2S levels. Mucosal barrier integrity was not considerably affected by H2S. Mucus metabolomes of the skin and gills were unaffected, but a matrix-dependent response was identified. Comparing the high-concentration group's skin and gills mucus metabolomes identified altered amino acid biosynthesis and metabolism pathways. The skin and gill mucus exhibited distinct proteomic profiles. Enrichment analysis revealed that proteins related to immunity and metabolism were affected in both mucus matrices. The present study expands our knowledge of the defence mechanisms against H2S at mucosal sites in Atlantic salmon. The findings offer insights into the health and welfare consequences of sub-lethal H2S, which can be incorporated into the risk assessment protocols in salmon land-based farms.

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Immunocompromised children are at risk of developing severe COVID-19 infection. We conducted a pilot prospective study to evaluate the impact of cancer treatment and stem cell transplantation on immunogenicity of two doses of BNT162b2 vaccine in pediatric patients.Humoral, B- and T-cell responses to the BNT162b2 vaccine were assessed before, after the first and the second dose in patients aged 5–12 years (n = 35) and in a group of healthy donors (HD, n = 12). Patients were divided in three groups: solid tumors (ST, n = 11), hematological malignancies (HM, n = 14) and Hematopoietic Stem Cell Transplantation (HSCT) recipients (n = 10). After two vaccine doses, the seroconversion rate was 79.3 % (72.7 % in ST, 66.7 % in HM and 100 % in HSCT). The antibodies production was not associated to the presence of memory B and T-cells. Memory B-cells were measurable in 45.5 % ST, 66.6 % HSCT and in 22.0 % HM. The specific T-cell response was observed in most ST (81.8 %) and HSCT (85.7 %) patients and at lesser extent in those with HM (55.5 %). The combination of all immunological parameters (antibodies, memory B and T cells) showed that a significant fraction of HM (33.3 %) and ST (18.2 %) patients completely failed to respond to vaccination. Although able to produce antibodies, 11.1 % of HM and 27.3 % of ST had no B- and T-cell memory. HSCT subgroup showed the best immune function, with 80 % complete response and optimal T-cell function.Combination of anti-RBD antibody, and specific memory B- and T-cell responses represents a reliable read-out of vaccine immune efficacy in frail patients.

Background: The main purpose was to determine the impact on postoperative outcomes of a standardized enhanced recovery program (ERP) for elective colorectal surgery in a rural hospital. Methods: A prospective series of patients (N = 80) undergoing elective colorectal resection completing a standardized ERP protocol in 2018–2020 (ERP group) was compared to patients (N = 80) operated at the same rural hospital in 2013–2015 (pre-ERP group), before the implementation of the program. The exclusion criteria for both groups were: ASA score IV, TNM stage IV, inflammatory bowel disease, emergency surgery, and rectal cancer. The primary outcome was hospital length of stay (LoS) which was used as an estimate of functional recovery. Secondary outcomes included 30-day readmission and mortality rates as well as associated factors with both postoperative complications and prolonged hospital LoS. Results: Baseline characteristics were comparable in both groups. The median adherence to ERP protocol elements was 68 % versus 12 % in the retrospective control group. The median hospital LoS in the ERP-group was significantly lower than in the pre-ERP group (5 vs. 10 days) with no increase in 30-day readmission and mortality rates. The Body Mass Index ≥30 and the traditional peri-operative protocol were the associated factors to postoperative complications, while following a traditional peri-operative protocol was the only factor associated with a prolonged hospital LoS (p

Summary: Homologous recombination is initiated by the nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection is a two-step process. In the short-range step, the MRX (Mre11-Rad50-Xrs2) complex, together with Sae2, incises the 5′-terminated strand at the DSB end and resects back toward the DNA end. Then, the long-range resection nucleases Exo1 and Dna2 further elongate the resected DNA tracts. We found that mutations lowering proteasome functionality bypass the need for Sae2 in DSB resection. In particular, the dysfunction of the proteasome subunit Rpn11 leads to hyper-resection and increases the levels of both Exo1 and Dna2 to such an extent that it allows the bypass of the requirement for either Exo1 or Dna2, but not for both. These observations, along with the finding that Exo1 and Dna2 are ubiquitylated, indicate a role of the proteasome in restraining DSB resection by negatively controlling the abundance of the long-range resection nucleases.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1–157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7–174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977–0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.