{\textless}sec{\textgreater}{\textless}title{\textgreater}Introduction{\textless}/title{\textgreater}{\textless}p{\textgreater}The colonization of patients by carbapenemase-producing {\textless}italic{\textgreater}Enterobacterales{\textless}/italic{\textgreater} ({CPE}) has been associated with heightened mortality, especially in vulnerable individuals within intensive care units ({ICUs}). Our study aimed to comprehensively assess {CPE} prevalence among {ICU} patients across the Mediterranean region pre-{COVID}-19, conducting a multicenter prevalence study in the first quarter of 2019.{\textless}/p{\textgreater}{\textless}/sec{\textgreater}{\textless}sec{\textgreater}{\textless}title{\textgreater}Methods{\textless}/title{\textgreater}{\textless}p{\textgreater}We collected clinical data and rectal or fecal samples from 256 {ICU} patients for {CPE} testing. Additionally, we performed whole-genome sequencing on 40 representative {CPE} strains to document their molecular characteristics.{\textless}/p{\textgreater}{\textless}/sec{\textgreater}{\textless}sec{\textgreater}{\textless}title{\textgreater}Results{\textless}/title{\textgreater}{\textless}p{\textgreater}Among the 256 patients, {CPE} was detected in 73 samples (28.5%), with prevalence varying from 3.3 to 69.0% across participating centers. We observed 13 colistin-resistant {CPE} strains, affecting three {ICUs}. Genetic analysis revealed highly diverse {\textless}italic{\textgreater}E. coli{\textless}/italic{\textgreater} and {\textless}italic{\textgreater}K. pneumoniae{\textless}/italic{\textgreater} strains, predominantly from international high-risk clones. Notably, {\textless}italic{\textgreater}bla{\textless}/italic{\textgreater}$_{\textrm{{OXA}-48}}$ and {\textless}italic{\textgreater}bla{\textless}/italic{\textgreater}$_{\textrm{{NDM}-1}}$ were the most prevalent carbapenemase genes. Molecular typing uncovered potential patient clusters in six centers. Significantly, longer hospital stays were associated with increased {CPE} carriage ({\textless}italic{\textgreater}p{\textless}/italic{\textgreater} < 0.001). Nine centers across Morocco, Tunisia, Egypt, and Lebanon voluntarily participated.{\textless}/p{\textgreater}{\textless}/sec{\textgreater}{\textless}sec{\textgreater}{\textless}title{\textgreater}Discussion{\textless}/title{\textgreater}{\textless}p{\textgreater}Our study provides {CPE} prevalence in Mediterranean {ICUs} and reaffirms established {CPE} presence in this setting but also provides updates on the molecular diversity of {CPE} strains. These findings highlight the imperative of reinforcing infection control measures in the participating {ICUs} to curtail escalated mortality rates, and of strictly applying isolation measures around patients originating from the Mediterranean region when transferred to other healthcare institutions.{\textless}/p{\textgreater}{\textless}/sec{\textgreater}

The objective of this work was to evaluate the suitability of carbohydrates and amino compounds in soil and soil organic matter (SOM) fractions to depict the management‐induced changes in soil over short‐term course. Soil samples were collected from two experimental fields managed according to organic farming regulations and a sequential fractionation procedure was applied to separate the light fraction (LF), particulate organic matter (POM), and mobile humic acid (MHA). Contents of carbohydrates and amino compounds were determined in soil and correspondent SOM fractions. Over a 2‐year course, carbohydrate contents decreased in the LF fraction while it increased noticeably in the POM and slightly in the MHA fractions leading into questioning whether decomposing materials get incorporated into older fractions. Amino N content constituted up to 30% of total soil N, with a major contribution of the humic fraction (MHA). Although the LF, POM, and MHA fractions showed the greatest amino N content after the compost‐legumes combinations, the carbohydrate and amino N contents in the POM and MHA fractions of the unamended soil increased as large as the corresponding fertilized plots, underlining that conservative soil management results in accumulation of labile forms of soil C and N that consequently might build up soil fertility. The changes after different treatments suggest the suitability of carbohydrates and amino compounds as short‐term indicators for soil management.

INTRODUCTION: Erectile dysfunction (ED) is common and considered to be predominantly of vascular origin. AIM: To evaluate the link between ED and coronary artery disease (CAD) and provide a consensus report regarding evaluation and management. METHODS: A committee of eight experts from six countries was convened to review the worldwide literature concerning ED and CAD and provide a guideline for management. MAIN OUTCOME MEASURE: Expert opinion was based on grading the evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. RESULTS: ED and CAD frequently coexist. Between 50-70% of men with CAD have ED. ED can arise before CAD is symptomatic with a time window of 3-5 years. ED and CAD share the same risk factors, and endothelial dysfunction is the common denominator. Treating ED in cardiac patients is safe, provided that their risks are properly evaluated. CONCLUSION: ED is a marker for silent CAD that needs to be excluded. Men with CAD frequently have ED that can be treated safely following guidelines.

Polymeric nanoparticles (NPs) are produced using bio-compatible and bio-degradable materials such as PLGA (Poly(lactic-co-glycolic acid)). This technology provides a valuable tool to deliver molecules to the subcellular level with a relatively low risk of cytotoxicity. However their use in the field of reproductive biotechnology is not yet scientifically substantiated. The aim of the present study was to test if PLGA NPs can be taken-up by cumulus-enclosed oocytes as a first step towards potential oocyte-targeted applications to enhance oocyte quality and fertility. We conducted a series of experiments using bovine in vitro oocyte maturation as a model to study FITC-conjugated PLGA internalization (using laser-scanning confocal microscopy) and the effect of some important physical (particle size) and chemical (conjugation with PEG) modifications. We show evidence that PLGA NPs can be taken-up by cumulus cells and to a less extent by the enclosed oocytes regardless of the NP size. The NP transfer to the oocyte appear to be transcellular (via cumulus cells and transzonal projections) and paracellular (via zona pellucida). The PLGA NPs were detected in the vicinity of the oocyte as quick as 2 h post-exposure in a protein-free medium and did not compromise cumulus cell viability nor subsequent early embryo development or embryo quality. These results suggest that PLGA NPs may have promising applications as carriers for drug or molecule delivery targeting cumulus cells and oocytes.

Amino acids (AAs) and peptides are thought to be part of humic acids (HAs) but debate whether they are an integral part of the HAs is still going. Humic acids sequentially extracted from peat and sod-podzolic soil were analyzed for their AAs content, elemental composition and by FTIR spectroscopy. Extracted HAs were hydrolyzed in 6 M HCl for 16 h for AAs release, which was detected by capillary electrophoresis system. Alanine, arginine, sum of aspartic acid and asparagine, sum of cysteic acid and cysteine, sum of glutamic acid and glutamine, glycine, histidine, leucine and isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, valine were identified. The total content of hydrolysable AAs in sod-podzol HAs increased by 6.2–8.2% with increasing the extraction cycles while an inverse tendency was observed for AAs released from peat HAs. Moreover, individual AAs expressed as percentages of total AAs were constant values with coefficients of variation lower than 20% for the studied HAs.

Botulinum toxin type A (BTX-A) is a frequently used therapeutic tool to denervate muscles in the treatment of neuromuscular disorders. Although considered safe by the US Food and Drug Administration, BTX-A can produce adverse effects in target and non-target muscles. With an increased use of BTX-A for neuromuscular disorders, the effects of repeat injections of BTX-A on strength, muscle mass and structure need to be known. Therefore, the purpose of this study was to investigate the changes in strength, muscle mass and contractile material in New Zealand White (NZW) rabbits. Twenty NZW rabbits were divided into 4 groups: control and 1, 3 and 6 months of unilateral, repeat injections of BTX-A into the quadriceps femoris. Outcome measures included knee extensor torque, muscle mass and the percentage of contractile material in the quadriceps muscles of the target and non-injected contralateral hindlimbs. Strength in the injected muscles was reduced by 88%, 89% and 95% in the 1, 3 and 6 months BTX-A injected hindlimbs compared to controls. Muscle mass was reduced by 50%, 42% and 31% for the vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM), respectively, at 1 month, by 68%, 51% and 50% at 3 months and by 76%, 44% and 13% at 6 months. The percentage of contractile material was reduced for the 3 and 6 months animals to 80-64%, respectively, and was replaced primarily by fat. Similar, but less pronounced results were also observed for the quadriceps muscles of the contralateral hindlimbs, suggesting that repeat BTX-A injections cause muscle atrophy and loss of contractile tissue in target muscles and also in non-target muscles that are far removed from the injection site.

Organic farming can overcome the environmental consequences of intensive conventional farming. The objective of the work was to investigate the changes in labile soil organic matter (SOM) fractions during the conversion from conventional to organic farming in two Italian sites, namely Foggia (FG) and Metaponto (MT), that differed mainly in initial soil organic carbon (SOC) content. Fields were cultivated with lentil and wheat in rotation and treated with either: i) compost or ii) nitrogen or phosphorus (N/P) fertilizers in three field replicates. The SOM was sequentially fractionated into light fraction (LF), particulate organic matter (POM) and mobile humic acid (MHA) fraction. Isolated fractions were quantified and analyzed for C and N contents. Although total SOC responded to the fertilization treatments, the LF and POM fractions were yet more responsive. The MHA represented on average 15% of SOC at both sites, however, the LF represented only 5–6% of total SOC but was the most responsive to changes in soil management. Compost application contributed significantly greater quantities of LF, POM and MHA than did the N/P fertilizers application. The initial SOC content can play an important role in determining the impacts of introducing organic farming practices on SOM fractions. Although both sites had an initial low SOC content, the MT site, with a lower SOC content, showed a substantial fractional C increments as compared to the FG site.

OBJECTIVE: To characterise patients with and without prevalent hypertension and COVID-19 and to assess adverse outcomes in both inpatients and outpatients.

DESIGN AND SETTING: This is a retrospective cohort study using 15 healthcare databases (primary and secondary electronic healthcare records, insurance and national claims data) from the USA, Europe and South Korea, standardised to the Observational Medical Outcomes Partnership common data model. Data were gathered from 1 March to 31 October 2020.

PARTICIPANTS: Two non-mutually exclusive cohorts were defined: (1) individuals diagnosed with COVID-19 (diagnosed cohort) and (2) individuals hospitalised with COVID-19 (hospitalised cohort), and stratified by hypertension status. Follow-up was from COVID-19 diagnosis/hospitalisation to death, end of the study period or 30 days.

OUTCOMES: Demographics, comorbidities and 30-day outcomes (hospitalisation and death for the 'diagnosed' cohort and adverse events and death for the 'hospitalised' cohort) were reported.

RESULTS: We identified 2 851 035 diagnosed and 563 708 hospitalised patients with COVID-19. Hypertension was more prevalent in the latter (ranging across databases from 17.4% (95% CI 17.2 to 17.6) to 61.4% (95% CI 61.0 to 61.8) and from 25.6% (95% CI 24.6 to 26.6) to 85.9% (95% CI 85.2 to 86.6)). Patients in both cohorts with hypertension were predominantly >50 years old and female. Patients with hypertension were frequently diagnosed with obesity, heart disease, dyslipidaemia and diabetes. Compared with patients without hypertension, patients with hypertension in the COVID-19 diagnosed cohort had more hospitalisations (ranging from 1.3% (95% CI 0.4 to 2.2) to 41.1% (95% CI 39.5 to 42.7) vs from 1.4% (95% CI 0.9 to 1.9) to 15.9% (95% CI 14.9 to 16.9)) and increased mortality (ranging from 0.3% (95% CI 0.1 to 0.5) to 18.5% (95% CI 15.7 to 21.3) vs from 0.2% (95% CI 0.2 to 0.2) to 11.8% (95% CI 10.8 to 12.8)). Patients in the COVID-19 hospitalised cohort with hypertension were more likely to have acute respiratory distress syndrome (ranging from 0.1% (95% CI 0.0 to 0.2) to 65.6% (95% CI 62.5 to 68.7) vs from 0.1% (95% CI 0.0 to 0.2) to 54.7% (95% CI 50.5 to 58.9)), arrhythmia (ranging from 0.5% (95% CI 0.3 to 0.7) to 45.8% (95% CI 42.6 to 49.0) vs from 0.4% (95% CI 0.3 to 0.5) to 36.8% (95% CI 32.7 to 40.9)) and increased mortality (ranging from 1.8% (95% CI 0.4 to 3.2) to 25.1% (95% CI 23.0 to 27.2) vs from 0.7% (95% CI 0.5 to 0.9) to 10.9% (95% CI 10.4 to 11.4)) than patients without hypertension.

CONCLUSIONS: COVID-19 patients with hypertension were more likely to suffer severe outcomes, hospitalisations and deaths compared with those without hypertension.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.

METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs.

RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%).

CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

BACKGROUND: Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination.

METHODS: A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio.

RESULTS: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs.

CONCLUSION: This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.

OBJECTIVE: To characterize 414 patients with primary SS who developed hematological malignancies and to analyze how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes.

METHODS: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Hematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified.

RESULTS: There were 414 patients (355 women, mean age 57 years) with hematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). 376 (91%) patients had mature B cell malignancy, nearly half MALT lymphoma (n = 197), followed by DLBCL (n = 67), nodal MZL lymphoma (n = 29), CLL/SLL (n = 19) and follicular lymphoma (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL).

CONCLUSION: In the largest reported study of hematological malignancies complicating primary SS, we confirm the overwhelming predominance of B cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

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