Intraspecific variability of leaf form and function across habitat types.

Trait-based ecology has already revealed main independent axes of trait variation defining trait spaces that summarize plant adaptive strategies, but often ignoring intraspecific trait variability (ITV). By using empirical ITV-level data for two independent dimensions of leaf form and function and 167 species across five habitat types (coastal dunes, forests, grasslands, heathlands, wetlands) in the Italian peninsula, we found that ITV: (i) rotated the axes of trait variation that define the trait space; (ii) increased the variance explained by these axes and (iii) affected the functional structure of the target trait space. However, the magnitude of these effects was rather small and depended on the trait and habitat type. Our results reinforce the idea that ITV is context-dependent, calling for careful extrapolations of ITV patterns across traits and spatial scales. Importantly, our study provides a framework that can be used to start integrating ITV into trait space analyses.

Bacterial and fungal superinfections are detected at higher frequency in critically ill patients affected by SARS CoV-2 infection than negative patients and are associated to a worse outcome.

Patients with viral infections are at higher risk to acquire bacterial and fungal superinfections associated with a worse prognosis. We explored this critical point in the setting of patients with severe COVID-19 disease. The study included 1911 patients admitted to intensive care unit (ICU) during a 2-year study period (March 2020-March 2022). Of them, 713 (37.3%) were infected with SARS-CoV-2 and 1198 were negative (62.7%). Regression analysis was performed to determine risk factors associated with the presence of bacterial and/or fungal superinfections in SARS-CoV-2 patients and to evaluate predictors of ICU mortality. Of the 713 patients with SARS-CoV-2 infection, 473 (66.3%) had respiratory and/or bloodstream bacterial and/or fungal superinfections, while of the 1198 COVID-19-negative patients, only 369 (30%) showed respiratory and/or bloodstream bacterial and/or fungal superinfections (p < 0.0001). Baseline characteristics of COVID-19 patients included a median age of 66 (interquartile range [IQR], 58-73), a predominance of males (72.7%), and the presence of a BMI higher than 24 (median 26; IQR, 24.5-30.4). Seventy-four percent (527, 73.9%) had one or more comorbidities and 135 (18.9%) of them had received previous antibiotic therapy. Furthermore, most of them (473, 66.3%) exhibited severe radiological pictures and needed invasive mechanical ventilation. Multivariate logistic regression analysis showed that 1 unit increment in BMI rises the risk of bacterial and/or fungal superinfections acquisition by 3% and 1-day increment in ICU stays rises the risk of bacterial and/or fungal superinfections acquisition by 11%. Furthermore, 1-day increment in mechanical ventilation rises the risk of bacterial and/or fungal superinfection acquisition by 2.7 times. Furthermore, patients with both bacterial and fungal infections had a significantly higher mortality rate than patients without superinfections (45.8% vs. 26.2%, p < 0.0001). Therefore, bacterial and fungal superinfections are frequent in COVID-19 patients admitted to ICU and their presence is associated with a worse outcome. This is an important consideration for targeted therapies in critically ill SARS-CoV-2 infected patients to improve their clinical course.

First Italian report of a liver abscess and metastatic endogenous endophthalmitis caused by ST-23 hypervirulent Klebsiella pneumoniae in an immunocompetent individual.

BACKGROUND: Klebsiella pneumoniae is a common species in the gut of mammals and is widely distributed in the environment. However, the environmental source of hvKp that precedes gut colonization is unclear, but once that it reaches the gut there is a possible generalized spread y fecal-oral transmission especially in endemic areas. Liver abscess might develop when the bacteria, using its virulence factors, cross the intestinal barrier and invade the liver by the portal circulation. This syndrome, prevalent mostly in Asian countries, is increasingly reported in Western Countries and leaves open questions about the source of infection. CASE: Here we describe for the first time in Italy, a case of pyogenic liver abscess caused by a hypervirulent Klebsiella pneumoniae (HvKp) complicated by endophthalmitis and other metastatic infections in lung and prostate in an immunocompetent Chinese healthy individual with no recent travel in Asia. CONCLUSION: This case underlines the need for increased awareness of hypervirulent K. pneumoniae, even in settings where it occurs infrequently and where there are not evident epidemiological links.

Strongyloides stercoralis infection: an underlying cause of invasive bacterial infections of enteric origin. Results from a prospective cross-sectional study of a northern Italian tertiary hospital.

PURPOSE OF THE STUDY: We assessed the prevalence of S. stercoralis in a cohort of inpatients with invasive bacterial infections of enteric origin to investigate whether the parasite may facilitate these bacterial infections even in the absence of larval hyperproliferation. METHODS: We performed a prospective cross-sectional study in a hospital in northern Italy. Subjects admitted due to invasive bacterial infection of enteric origin and potential previous exposure to S. stercoralis were systematically enrolled over a period of 10 months. S. stercoralis infection was investigated with an in-house PCR on a single stool sample and with at least one serological method (in-house IFAT and/or ELISA Bordier). Univariate, bi-variate and logistic regression analyses were performed. RESULTS: Strongyloidiasis was diagnosed in 14/57 patients (24.6%; 95% confidence interval 14.1-37.8%) of which 10 were Italians (10/49, 20.4%) and 4 were migrants (4/8, 50.0%). Stool PCR was performed in 43/57 patients (75.4%) and no positive results were obtained. Strongyloidiasis was found to be significantly associated (p ≤ 0.05) with male gender, long international travels to areas at higher endemicity, deep extra-intestinal infectious localization and solid tumors. In the logistic regression model, increased risk remained for the variables deep extra-intestinal infectious localization and oncologic malignancy. CONCLUSIONS: Our findings suggest a new role of chronic strongyloidiasis in favoring invasive bacterial infections of enteric origin even in the absence of evident larval dissemination outside the intestinal lumen. Further well-designed studies should be conducted to confirm our results, and possibly establish the underlying mechanisms.

Cost-analysis of persistent hyperkalaemia in non-dialysis chronic kidney disease patients under nephrology care in Italy.

AIM: In patients with chronic kidney disease (CKD), hyperkalaemia (HK) (potassium level ≥ 5.0 mEq/L) is associated with poor clinical outcomes. This study provides novel insights by comparing management costs of CKD patients with normokalaemia vs those with persistent HK regularly followed in renal clinics in Italy. METHODS: To this aim, a Markov model over life-time horizon was developed. Time to end-stage renal disease (ESRD) and time to death in CKD patients were derived from an observational multi-centre database including 1665 patients with non-dialysis CKD stage 1-5 under nephrology care in Italy (15 years follow-up). Resource use for CKD and HK management was obtained from the observational database, KDIGO international guidelines, and clinical expert opinion. RESULTS: Results showed that patients with normokalaemia vs persistent HK brought an average per patient lifetime cost-saving of €16 059 besides delayed onset of ESRD by 2.29 years and increased survival by 1.79 years with increment in total survival and dialysis-free survival in normokalaemia that decreased from early to advanced disease. Cost-saving related to normokalaemia increased at more advanced CKD; however, it was already evident at early stage (3388.97€ at stage 1-3a). OWSA confirmed cost-saving associated with normokalaemia across all parameter variations. DISCUSSION AND CONCLUSION: This model is the first to simulate the impact of HK in non-dialysis CKD patients on economic and clinical outcomes using real-world data from nephrology clinics. In these patients, persistent HK results into higher lifetime costs, besides poorer clinical outcomes, that are evident since the early stages of CKD. Maintaining normokalaemia should therefore be of main concern in CKD treatment planning to improve long-term economic and clinical outcomes.

Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency.

Hermansky-Pudlak syndrome type 2 (HPS2) is a primary immunodeficiency due to adaptor protein-3 (AP-3) complex deficiency. HPS2 patients present neutropenia, partial albinism, and impaired lysosomal vesicles formation in hematopoietic cells. Given the role of dendritic cells (DCs) in the immune response, we studied monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs) in two HPS2 siblings. Mature HPS2 moDCs showed impaired expression of CD83 and DC-lysosome-associated membrane protein (LAMP), low levels of MIP1-ß/CCL4, MIG/CXCL9, and severe defect of interleukin-12 (IL-12) secretion. DCs in lymph-node biopsies from the same patients showed a diffuse cytoplasm reactivity in a large fraction of DC-LAMP(+) cells, instead of the classical dot-like stain. In addition, analysis of pDC-related functions of blood-circulating mononuclear cells revealed reduced interferon-α secretion in response to herpes simplex virus-1 (HSV-1), whereas granzyme-B induction upon IL-3/IL-10 stimulation was normal. Finally, T-cell costimulatory activity, as measured by mixed lymphocyte reaction assay, was lower in patients, suggesting that function and maturation of DCs is abnormal in patients with HPS2.

Streptococcus Pneumoniae Detection Long Time After Death in a Fatal Case of Waterhouse-Friderichsen Syndrome.

We report a fatal case of Waterhouse-Friderichsen syndrome in a 64-year-old man. The diagnosis, suspected during the autopsy (performed 63 hours after death), was confirmed through the successful detection of Streptococcus pneumoniae DNA and antigens in samples (blood and liver) collected during the autopsy. These results conformed with blood cultures performed antemortem, which became available only the day after the autopsy. The case underlines the need to collect biological material (liver and blood samples) during autopsy for microbiological investigations, although the collection is performed a long time after the death, suggesting that a liver sample works for DNA and liver and blood work for Streptococcus pneumoniae antigen detection.

Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for identification and clustering of Neisseria gonorrhoeae.

BACKGROUND: The sexually transmitted infection gonorrhea remains a public health concern for becoming resistant to drug treatments available. The purpose of this study was to evaluate the usefulness of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify and cluster Neisseria gonorrhoeae. From a current monitoring in Italy, as part of the European Gonococcal Antimicrobial Surveillance Programme (EURO-GASP), 93 gonococci collected from 2007 to 2012 susceptible (44 isolates) and resistant (49 isolates) to cefixime were selected. Minimum Inhibitory Concentration (MIC) values for cefixime was assessed by Etest carried out in agreement with the manufacturer's instructions and interpreted referring to European Committee on Antimicrobial Susceptibility testing (EUCAST) clinical breakpoints criteria. Data obtained by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and the dendrogram based on the concatenation of porB and tbpB genes were evaluated. MALDI-TOF MS, to reconfirm gonorrhea identification, analyzed single colonies from freshly grown isolates and applied directly on a ground-steel MALDI target plate. For the MALDI-TOF dendrogram cluster analysis, MSPs (Main Spectrum Profile) from each isolate were created acquiring 5000 shots from 10 technical replicates obtained from bacteria extraction. RESULTS: Molecular typing by NG-MAST showed 28 sequence types (STs); G1407 was the predominant accounting for 75 gonococci. All the 93 gonococci, except one, were correctly identified at species level by MALDI-TOF MS and G1407 isolates were divided into two clusters. CONCLUSION: MALDI-TOF MS for a real-time detection and cluster analysis of gonorrhea is a promising tool for surveillance purposes. Moreover, additional studies are required to collect more data on the performance of MALDI-TOF MS for gonococci.

Chlamydia trachomatis genotypes in school adolescents, Italy.

Chlamydia trachomatis genogroups using ompA and multilocus sequence typing (MLST) were determined in consecutive isolates from school students aged 18 or older in the district of Brescia, Italy, 2012-2013. Among 40 samples, 4 ompA genovars and 18 STs were identified. Genovar E predominated (70 %) including five STs derived from ST59 (29 % of all isolates). This study, combining ompA and MLST typing of C. trachomatis school teenagers, suggests limited mixing and sexual interchange in this population.

Clinical course of chronic hepatitis B patients receiving nucleos(t)ide analogues after virological breakthrough during monotherapy with lamivudine.

Little is known about the optimal management of patients with chronic hepatitis B (CHB) who develop drug resistance. The aim of this study was to investigate the effectiveness of different drug regimens in chronically HBV-infected patients. HBV viral load was determined using a bDNA assay and the substitutions in HBV-DNA were studied by polymerase sequencing test. The study involved 38 patients who experienced a therapeutic failure to lamivudine (LAM). The sequential treatments used were: LAM + adefovir (ADV), LAM + tenofovir (TDF), entecavir (ETV) monotherapy, ADV monotherapy and TDF monotherapy. Similar activity against HBV replication was observed with all drug regimens. Of the patients treated with LAM, 44% developed resistance mutations. The rt M204I mutation was observed more frequently. Sequential ADV add-on LAM and TDF therapy induced the appearance of resistance in 3/18 (16.6%) and in 1/8 (5.5%) treated patients, respectively. Genotype D was the most prevalent (78.9%), followed by genotype A (13%), genotype E (5.2%) and genotype C (2.6%). Our study showed that baseline serum HBV DNA is an important predictor of virologic response and that virologic breakthrough is significantly associated with the insurgence of genotypic resistance.

In vitro activity of solithromycin against erythromycin-resistant Streptococcus agalactiae.

The in vitro antibacterial activity of solithromycin (CEM-101) against macrolide-resistant isolates (n=62) of Streptococcus agalactiae (group B streptococcus [GBS]) was determined. Phenotypic characterization of macrolide-resistant strains was performed by double-disc diffusion testing. A multiplex PCR was used to identify the erm(B), erm(TR), and mef(A/E) genes, capsular genotypes, and alpha-like (Alp) protein genes from the GBS strains. Determination of MIC was carried out using the microdilution broth method. The Etest method was used for penicillin, azithromycin, clarithromycin, and erythromycin. Solithromycin had a MIC50 of ≤0.008 µg/ml and a MIC90 of 0.015 µg/ml against macrolide-susceptible S. agalactiae. These MICs were lower than those displayed by penicillin (MIC50 of 0.032 µg/ml and MIC90 of 0.047 µg/ml), the antibiotic agent of choice for prophylaxis and treatment of GBS infections. Against macrolide-resistant S. agalactiae, solithromycin had a MIC50 of 0.03 µg/ml and a MIC90 of 0.125 µg/ml. Against erm(B) strains, solithromycin had a MIC50 of 0.03 µg/ml and a MIC90 of 0.06 µg/ml, while against mef(A) strains, it had a MIC50 of 0.03 µg/ml and a MIC90 of 0.125 µg/ml. Most erythromycin-resistant GBS strains were of serotype V (64.5%) and associated significantly with alp2-3. Moreover, a statistically significant association was observed between the constitutive macrolide-lincosamide-streptogramin B resistance (cMLSB) phenotype and the erm(B) gene-carrying strains, the alp2-3 gene and the M phenotype, and the mef(A/E) gene and epsilon. Overall, our results show that solithromycin had lower or similar MICs than penicillin and potent activity against macrolide-resistant strains independent of their genotype or phenotype, representing a valid therapeutic alternative where ß-lactams cannot be used.

Economic evaluation of intravenous iodinated contrast media in Italy.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is defined as a deterioration in renal function after administration of radiologic iodinated contrast media (CM). Iodixanol, showed a lower CI-AKI incidence than low-osmolar contrast media (LOCM). A cost-effectiveness analysis was performed comparing iodixanol and LOCM in intravenous (IV) setting in Italy. METHODS: A Markov model was developed. Patients moved across four health states: CI-AKI free, CI-AKI, myocardial infarction, and death. The simulation horizon was lifetime with 1-month cycles. Costs and outcomes were discounted at 3.5 percent rate. CI-AKI incidence was considered from published literature across different definitions. Cost-effectiveness of iodixanol was assessed in terms of incremental cost per life-year gained. Net monetary benefit (NMB) was also calculated. Both deterministic and probabilistic sensitivity analyses were performed. RESULTS: Base-case results showed an average survival increase of 0.51 life-years and a savings of €7.25 for iodixanol versus LOCM. The cost-effectiveness of iodixanol was confirmed when other scenarios were explored, such as varying CI-AKI definition, sub-populations with specified risk factors, CM hospital bids prices, and inclusion of adverse drug reactions of allergic nature. An NMB ranging between €6,007.25 and €30,007.25 was calculated. CONCLUSION: Base-case results show that IV iodixanol is cost-effective compared with LOCM in the Italian clinical setting of a hospital computed tomography radiology practice. However, some caution is due, mainly linked to inherent limitations of the modeling technique and to the lack of agreement on CI-AKI incidence data in the clinical literature.

Emergence of carbapenem-resistant Klebsiella Pneumoniae strains producing KPC-3 in Brescia Hospital, Italy.

Carbapenem-resistant K. pneumoniae has recently been reported as a new multidrug-resistant nosocomial pathogen. This study reports the emergence of carbapenem-resistant K. pneumoniae strains in Brescia Civic Hospital, Italy. Different samples, collected from April 2012 to February 2013, showed that 29 patients presented infections from multidrug-resistant K. pneumoniae and three of these patients were intestinal carriers. In total, 40 carbapenem-resistant K. pneumoniae strains were isolated from multiple specimens of these patients. In 39 out of 40 samples, we identified the bla(KPC-3) carbapenemase gene variant responsible for bacterial carbapenem resistance. The DiversiLab analysis showed four different genetic patterns within multidrug-resistant K. pneumoniae isolates, with pattern 1 and 2 including 95% of the bacterial strains. Carbapenem-resistant K. pneumoniae strains belonging to patterns 1 and 2 were also detected in the intestinal tract of the three asymptomatic carriers. Moreover, isolation of the same strains in other body sites of the same patients and in bronchial fluid of a non-colonized patient in the same ward indicates an initial dissemination of this pathogen. Our results highlight the emergence of carbapenemase-producing K. pneumoniae strains in different hospital wards and the urgent need for infection control, antibiotic stewardship programmes and utilization of a surveillance and prevention system.

Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?

Alzheimer's disease and Parkinson's disease represent the most common forms of cognitive impairment. Multiple sclerosis is a chronic inflammatory disease of the central nervous system responsible for severe disability. An aberrant immune response is the cause of myelin destruction that covers axons in the brain, spinal cord, and optic nerves. Systemic lupus erythematosus is an autoimmune disease characterized by alteration of B cell activation, while Sjögren's syndrome is a heterogeneous autoimmune disease characterized by altered immune responses. The etiology of all these diseases is very complex, including an interrelationship between genetic factors, principally immune associated genes, and environmental factors such as infectious agents. However, neurodegenerative and autoimmune diseases share proinflammatory signatures and a perturbation of adaptive immunity that might be influenced by herpesviruses. Therefore, they might play a critical role in the disease pathogenesis. The aim of this review was to summarize the principal findings that link herpesviruses to both neurodegenerative and autoimmune diseases; moreover, briefly underlining the potential therapeutic approach of virus vaccination and antivirals.

Immunogenicity and safety of live attenuated and recombinant/inactivated varicella zoster vaccines in people living with HIV: A systematic review.

Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.

Amoebic colitis and liver abscess: A rare case of autochthonous invasive infection due to Entamoeba histolytica.

We report an unusual and confirmed case of invasive amebiasis in a non-endemic area where the source of infection remains unknown. During her admission, the patient developed amebic colitis and extraintestinal liver abscess with a favorable outcome following the antiparasitic therapy.

Efgartigimod and Ravulizumab for Treating Acetylcholine Receptor Auto-antibody-Positive (AChR-Ab+) Generalized Myasthenia Gravis: Indirect Treatment Comparison.

INTRODUCTION: Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been directly compared. This paper assessed comparative effects of efgartigimod vs. ravulizumab for treating adults with AChR-Ab+ gMG using indirect treatment comparison methods. METHODS: The matching-adjusted indirect comparison used data from two randomized trials of adult men and women. The ADAPT (efgartigimod vs. placebo; individual patient data available) population was reweighted to match the CHAMPION (ravulizumab vs. placebo; index study; aggregate data available) population. The relative effect of efgartigimod versus placebo was estimated in this reweighted population and compared with the observed ravulizumab versus placebo effect to estimate the efgartigimod versus ravulizumab effect. The outcomes were Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r) assessed as cumulative effect (area under the curve; AUC) over 26 weeks (primary) and change from baseline at 4 weeks and time of best response (week 4 for efgartigimod; week 26 for ravulizumab). RESULTS: For MG-QoL15r, efgartigimod had a statistically significant improvement compared with ravulizumab over 26 weeks [mean difference (95% confidence interval): - 52.6 (- 103.0, - 2.3)], at week 4 [- 4.0 (- 6.6, - 1.4)], and at time of best response [- 3.9 (- 6.5, - 1.3)]. Efgartigimod had a statistically significant improvement over ravulizumab in MG-ADL at week 4 [- 1.9 (- 3.3, - 0.5)] and at time of best response [- 1.4 (- 2.8, 0.0)] and in QMG at week 4 [- 3.2 (- 5.2, - 1.2)] and at time of best response [- 3.0 (- 5.0, - 1.0)]. For AUC over 26 weeks, improvements were not significantly different between efgartigimod and ravulizumab for MG-ADL [- 8.7 (- 36.1, 18.8)] and QMG [- 13.7 (- 50.3, 22.9)]. CONCLUSION: Efgartigimod may provide a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+ gMG. Efgartigimod showed faster improvements in MG-ADL and QMG than ravulizumab.

Incidence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum isolated in Brescia, Italy, over 7 years.

The prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis collected during 2004-2011 were determined. A total of 9956 individuals was analyzed. Identification was performed by use of the mycoplasma IST-2 kit. Antimicrobial susceptibility against doxycycline, josamycin, ofloxacin, erythromycin, tetracycline, ciprofloxacin, azithromycin, clarithromycin, and pristinamycin was also tested by use of this commercial kit. Our results show a prevalence of 1856 positive patients for genital mycoplasmas (18.6 %). Among positive cultures, 89 and 1.1 % of isolates were Ureaplasma urealyticum and Mycoplasma hominis, respectively. For 9.8 % of isolates both urogenital mycoplasmas were grown. Doxycycline was the most active tetracycline for mycoplasma infections, and this is still the drug of first choice. Among macrolides, josamycin and clarithromycin are the most active agents against ureaplasmas; josamycin is also active against mycoplasmas and is an alternative to tetracyclines and erythromycin for mixed infections, especially for pregnant women and neonates. Fluoroquinolones had low efficacy against urogenital mycoplasmas. For Ureaplasma urealyticum, cross-resistance was found between erythromycin and macrolides (except josamycin) (40-80 %) and between erythromycin and ciprofloxacin (79 %). Antibiotic resistance over the test period did not vary significantly. Because of geographical differences among antibiotic resistance, local in-vitro susceptibility testing is recommended to avoid failure of therapy.