Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art.

Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood-brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated.

Codium fragile (Suringar) Hariot as Biostimulant Agent to Alleviate Salt Stress in Durum Wheat: Preliminary Results from Germination Trials.

Soil salinization is a critical environmental problem in arid and semiarid regions of the world. The aim of the present study was to evaluate the effect of an algae-based biostimulant on germination and seedling vigour of durum wheat (Triticum turgidum L. subsp. durum (Desf.) Husn.), under different saline conditions (0, 100, and 200 mM NaCl). The experiment was carried out under controlled-environment conditions. Seeds were sprayed with a solution containing a combination of fungicide and different concentrations of Codium fragile (Suringar) Hariot algae (0%w/v, 10%w/v, 20%w/v, and 30%w/v). All experimental units were placed in a germination cabinet. The effect of the seaweed extract (SWE) on seed germination and seedling performance under salinity stress was evaluated over a period of 8 days. Coleoptile length and biomass were found to be significantly and positively affected by the application of different SWE doses as compared to the control treatment (0% algae). As for germination traits, seeds treated with SWE showed a final germination (from 82% to 88%), under severe saline conditions, significantly higher than that observed in the control treatment (61%). Our findings indicate that the appropriate dose of biostimulant can markedly improve the germination and the seedlings vigour of durum wheat seeds under saline conditions. Additional studies will be needed to understand the mechanism of action of this biostimulant and its effectiveness in longer studies under field conditions.

Trichosporon asahii Infective Endocarditis of Prosthetic Valve: A Case Report and Literature Review.

Trichosporon spp. endocarditis is a severe and hard-to-treat infection. Immunosuppressed subjects and carriers of prosthetic valves or intracardiac devices are at risk. This article presents the case of an immunocompetent 74-year-old man affected by endocarditis of the prosthetic aortic valve. After Bentall surgery, cultures of the removed valve demonstrated Trichosporon ashaii as the etiological agent. The patient was treated with amphotericin B at first and subsequently with fluconazole. Given the fragility of the patient and the aggressiveness of the pathogen, life-long prophylactic therapy with fluconazole was prescribed. After 5 years follow-up, no drug-related toxicities were reported and the patient never showed any signs of recurrence. The review of the literature illustrates that Trichosporon spp. endocarditis may present even many years after heart surgery, and it is often associated with massive valve vegetations, severe embolic complications, and unfavorable outcome. Due to the absence of international guidelines, there is no unanimous therapeutic approach, but amphotericin B and azoles are usually prescribed. Additionally, a prompt surgical intervention seems to be of paramount importance. When dealing with a life-threatening disease, such as mycotic endocarditis of prosthetic valves, it is essential to consider and treat even rare etiological agents such as Trichosporon spp.

Small "Nested" Introgressions from Wild Thinopyrum Species, Conferring Effective Resistance to Fusarium Diseases, Positively Impact Durum Wheat Yield Potential.

Today wheat cultivation is facing rapidly changing climate scenarios and yield instability, aggravated by the spreading of severe diseases such as Fusarium head blight (FHB) and Fusarium crown rot (FCR). To obtain productive genotypes resilient to stress pressure, smart breeding approaches must be envisaged, including the exploitation of wild relatives. Here we report on the assessment of the breeding potential of six durum wheat-Thinopyrum spp. recombinant lines (RLs) obtained through chromosome engineering. They are characterized by having 23% or 28% of their 7AL chromosome arm replaced by a "nested" alien segment, composed of homoeologous group 7 chromosome fractions from Th. ponticum and Th. elongatum (=7el1L + 7EL) or from different Th. ponticum accessions (=7el1L + 7el2L). In addition to the 7el1L genes Lr19 + Yp (leaf rust resistance, and yellow pigment content, respectively), these recombinant lines (RLs) possess a highly effective QTL for resistance to FHB and FCR within their 7el2L or 7EL portion. The RLs, their null segregants and well-adapted and productive durum wheat cultivars were evaluated for 16 yield-related traits over two seasons under rainfed and irrigated conditions. The absence of yield penalties and excellent genetic stability of RLs was revealed in the presence of all the alien segment combinations. Both 7el2L and 7EL stacked introgressions had positive impacts on source and sink yield traits, as well as on the overall performance of RLs in conditions of reduced water availability. The four "nested" RLs tested in 2020 were among the top five yielders, overall representing good candidates to be employed in breeding programs to enhance crop security and safety.

Effects of Environment and Sowing Time on Growth and Yield of Upland Cotton (Gossypium hirsutum L.) Cultivars in Sicily (Italy).

Cotton is one of the most important industrial crops in the world. Though widely cultivated in Sicily (Italy) in the past, cotton growth on the island has disappeared today due to a complex variety of agronomic, economic and socio-political reasons. In recent years, increased interest in natural fibers worldwide has led to a revival in cotton plants in the Mediterranean area. The aim of this paper was to assess the response of Gossypium hirsutum L. cultivars to different environments and sowing times. Elsa and Juncal were selected from the most promising cotton cultivars regarding earliness and productivity. Plants were tested with three sowing times and in two Sicilian environments. Cotton yield and yield components were significantly affected by experimental station, sowing time and cultivar. Lint yield of cultivars was 1.60 t ha-1 on average, and the highest value of 1.99 t ha-1 was obtained from an early sowing time. The three indices of agronomic earliness varied significantly based on treatments. In conclusion, the evaluation of response genotype-by-environment under different sowing times could represent a strategy to obtain optimal cotton seed and lint yields, although other general aspects, such as labor costs, land availability and capital resources, should be also considered when evaluating the reintroduction of the species in Sicily.

Equipping Durum Wheat-Thinopyrum ponticum Recombinant Lines With a Thinopyrum elongatum Major QTL for Resistance to Fusarium Diseases Through a Cytogenetic Strategy.

Prompted by recent changes in climate trends, cropping areas, and management practices, Fusarium head blight (FHB), a threatening disease of cereals worldwide, is also spreading in unusual environments, where bread wheat (BW) and durum wheat (DW) are largely cultivated. The scarcity of efficient resistance sources within adapted germplasm is particularly alarming for DW, mainly utilized for human consumption, which is therefore at high risk of kernel contamination by health-dangerous mycotoxins (e.g., deoxynivalenol = DON). To cope with this scenario, we looked outside the wheat primary gene pool and recently transferred an exceptionally effective FHB resistance QTL (Fhb-7EL) from Thinopyrum elongatum 7EL chromosome arm onto a Thinopyrum ponticum 7el1L arm segment, containing additional valuable genes (including Lr19 for leaf rust resistance and Yp for yellow pigment content), distally inserted onto 7DL of BW lines. Two such lines were crossed with two previously developed DW-Th. ponticum recombinants, having 7el1L distal portions on 7AL arms. Genomic in situ hybridization (GISH) analysis showed homologous pairing, which is enabled by 7el1L segments common to the BW and DW recombinant chromosomes, to occur with 42-78% frequency, depending on the shared 7el1L amount. Aided by 7EL/7el1L-linked markers, 7EL+7el1L tetraploid recombinant types were isolated in BC1 progenies to DW of all cross combinations. Homozygous 7EL+7el1L recombinant plants and null segregates selected in BC2F2 progenies were challenged by Fusarium graminearum spike inoculation to verify the Fhb-7EL efficacy in DW. Infection outcomes confirmed previous observations in BW, with >90% reduction of disease severity associated with Fhb-7EL presence vs. its absence. The same differential effect was detected on seed set and weight of inoculated spikes, with genotypes lacking Fhb-7EL having ∼80% reduction compared with unaffected values of Fhb-7EL carriers. In parallel, DON content in flour extracts of resistant recombinants averaged 0.67 ppm, a value >800 times lower than that of susceptible controls. Furthermore, as observed in BW, the same Fhb-7EL also provided the novel DW recombinants with resistance to Fusarium crown rot (∼60% symptom reduction) as from seedling infection with Fusarium culmorum. Through alien segment stacking, we succeeded in equipping DW with a very effective barrier against different Fusarium diseases and other positive attributes for crop security and safety.

Sowing Date and Seeding Rate Affect Bioactive Compound Contents of Chickpea Grains.

Chickpea grains may represent an alternative to soybean meals and energetic concentrates in animal feeding, as their nutritional value can help to increase the sustainability of livestock systems. Unfortunately, the presence of bioactive compounds with anti-nutritional effects can prevent its direct use, especially in mono-gastrics. It is known that the synthesis of these compounds depends on genetic expression, which is also influenced by growth conditions. The objective of this two-year study was to assess the effect of sowing date (winter versus spring) and seeding rate (70 versus 110 seeds m-2) on the accumulation of soluble carbohydrates, α-galactosides, trypsin inhibitors, and inositol phosphates in the grains of two Kabuli cultivars, in the Mediterranean climate. The results showed that seeds collected from winter sowing contained more trypsin inhibitors than those seeded in spring (+ 4%, on average), reaching values between 16.1 and 18.6 TIU mg protein-1. The seeding rate affects only the α-galactosides content, which increases (+9%) at lower densities (70 seeds m-2). These findings suggest that agronomic management can be used to modulate the content of some anti-nutritional factors in the seeds, even though the genetic characteristics and phenotypic expression, in relation to the climatic conditions, seem to deeply affect the content of all the bioactive compounds investigated.

Capsule enteroscopy vs. other diagnostic procedures in diagnosing obscure gastrointestinal bleeding: a cost-effectiveness study.

BACKGROUND: Capsule enteroscopy is considered the gold standard for evaluating patients with obscure gastrointestinal bleeding. The costs of capsule enteroscopy examination, however, make it uncertain whether the clinically relevant diagnostic gain is also associated with cost savings. AIM: To evaluate the incremental cost-effectiveness ratio of capsule enteroscopy in patients with obscure gastrointestinal bleeding. METHODS: Retrospective study was carried out in nine Italian gastroenterology units from 2003 to 2005. Data on 369 consecutive patients with obscure gastrointestinal bleeding were collected. The diagnostic yield of capsule enteroscopy vs. other imaging procedures was evaluated as a measure of efficacy. The values of Diagnosis Related Group 175 (euro 1884.00 for obscure-occult bleeding and euro 2141.00 for obscure-overt bleeding) were calculated as measures of economic outcomes in the cost analysis. RESULTS: Obscure and occult gastrointestinal bleeding was recorded in 177 patients (48%) with a mean duration of anemia history of 17.6+/-20.7 months. Among patients, 60.9% had had at least one hospital admission, 21.2% at least two, and 1.2% of obscure bleeders up to nine admissions. Overall, 58.4% of patients had positive findings with capsule enteroscopy compared with 28.0% with other imaging procedures (P<0.001). The mean cost of a positive diagnosis with capsule enteroscopy was euro 2090.76 and that of other procedures was euro 3828.83 with a mean cost saving of euro 1738.07 (P<0.001) for one positive diagnosis. CONCLUSIONS: Capsule enteroscopy is a cost-saving approach in the evaluation of patients with obscure gastrointestinal bleeding.

Enzyme and fungal treatments and a combination thereof reduce olive mill wastewater phytotoxicity on Zea mays L. seeds.

The phytotoxicity of olive-mill wastewater (OMW) has been suggested to be mainly due to its phenolic components. This study investigated the impact of three different low-cost dephenolization treatments on the wastewater phytotoxicity. To this aim, germinability of maize (Zea mays L.) seeds sown on a sandy-loamy soil which had been spread with different volumes (from 40 to 160m(3)ha(-1)) of either biologically-treated OMW or relative incubation control was determined. Biological treatments included either Panus tigrinus liquid cultures or incubation with commercial laccase (1UIml(-1)) or an innovative sequential combination of laccase and P. tigrinus cultures. All treatments markedly reduced phytotoxicity and promising results were obtained with commercial laccase. In fact, germinability and mean germination times in soil spread with laccase-treated OMW, did not significantly differ from those observed in soil irrigated with tap water (control) up to OMW volumes of 120m(3)ha(-1). Although the highest phenol reduction (ca. 81%) was obtained by the sequential use of laccase and P. tigrinus, the feasibility of the enzyme treatment is undoubtedly more convincing under the technological point of view.

Histologic risk factors and clinical outcome in colorectal malignant polyp: a pooled-data analysis.

PURPOSE: The malignant polyp carries a significant risk of lymphohematic metastasis and mortality. Clinical usefulness of histologic risk factors is still controversial. The study was designed to compute the association between the main histologic risk factors and the occurrence of unfavorable outcomes in patients with malignant polyps. METHODS: A MEDLINE search regarding malignant polyps was performed. Three histologic risk factors (positive resection margin, poor differentiation of carcinoma, vascular invasion) and five (residual disease, recurrent disease, lymph node metastasis, hematogenous metastasis, mortality) unfavorable clinical outcomes were evaluated. Further analysis was performed by subgrouping polyps in high-risk and low-risk groups. RESULTS: Thirty-one studies enrolling 1,900 patients with malignant polyp were selected. Positivity of resection margin was significantly predictive of the presence of residual disease (odds ratio, 22; P < 0.0001), poorly differentiated carcinoma was associated with an increased mortality (odds ratio, 9.2; P < 0.05), and vascular invasion with a higher lymph node metastasis risk (odds ratio, 7; P < 0.05). Patients with high-risk polyps showed a significantly worse outcome than those with low-risk, especially for mortality (odds ratio, 11; P < 0.05). Surgical-related death was as low as 0.8 percent. CONCLUSIONS: All three histologic risk factors are significantly associated with the clinical outcome. Classification in low-risk and high-risk patients may be regarded as a meaningful staging procedure.

Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases.

BACKGROUND & AIMS: Capsule endoscopy (CE) is a promising diagnostic tool for the study of patients with obscure gastrointestinal bleeding. However, the diagnostic yield of this technique has not been adequately studied. We evaluated sensitivity and specificity of CE and the outcome after CE in patients with obscure gastrointestinal bleeding. METHODS: One hundred consecutive patients (all with recent negative upper and lower endoscopy; 26 with ongoing overt bleeding [group A], 31 with previous overt bleeding [group B], and 43 with guaiac-positive stools and iron-deficiency anemia [group C]) underwent CE. RESULTS: The yield of positive findings on CE was 92.3% in group A, 12.9% in group B, and 44.2% in group C (P < 0.0001, A vs. B, A vs. C). Angiodysplasia (29%) and Crohn's disease (6%) were the most common diagnoses. Sensitivity, specificity, and positive and negative predictive values of CE were 88.9%, 95%, 97%, and 82.6%, respectively. CE results led to treatments resolving the bleeding in 86.9% of patients undergoing the procedure while actively bleeding. Capsule retention because of unsuspected stenosis occurred in 5 patients and required surgery, which resolved the clinical problem, in 4 patients. CONCLUSIONS: CE is an effective diagnostic tool for patients with obscure GI bleeding. The best candidates for the procedure are those with ongoing obscure-overt bleeding or with obscure-occult bleeding. If done early in the course of the workup, CE could shorten considerably the time to diagnosis, lead to definitive treatment in a relevant proportion of patients, and spare a number of alternative investigations with low diagnostic yield.

Reuse of microbially treated olive mill wastewater as fertiliser for wheat (Triticum durum Desf.).

Free cells of Aspergillus niger were grown on olive mill wastewater (OMW) supplemented with rock phosphate (RP) in an air-lift bioreactor in batch and repeated-batch processes. The fungus grew well and reduced the chemical oxygen demand of the waste by 35% and 64% in the batch and repeated-batch (fourth batch) processes, respectively. Total sugar content was consistently reduced (ca. 60%) in both processes while reduction of total phenols was minimal. RP was solubilised and maximum soluble P was 0.63 and 0.75 gl(-1) in the batch and repeated-batch (third batch), respectively. Several types of OMW+/-RP, microbially-treated or not, were tested in a greenhouse for their fertilising ability on a soil-wheat (Triticum durum Desf.) model system. Beneficial effects were highest using OMW treated by the repeated-batch process. The treated plants showed an increase in seed biomass, spike number, and kernel weight. Harvest index was highest (0.49+/-0.04) after treatment with OMW from the repeated-batch process.

Deletions of 17p are associated with transition from early to advanced colorectal cancer.

Several chromosome defects parallel morphologic evolution in colorectal tumor progression. Allelic losses in the short arm of chromosome 17, the majority encompassing the 17p13.3 band, have been found in advanced cancer in the absence of TP53 mutations, suggesting that loss of genes in this chromosome region is relevant for tumorigenesis. The aim of this study was to investigate 17p13.3 deletions throughout the colorectal tumor progression using two-color fluorescence in situ hybridization. Histologic sections from 20 colorectal adenomas containing early invasive carcinoma were analyzed by interphase fluorescence in situ hybridization using a centromeric probe for chromosome 17 simultaneously with a subtelomeric probe mapping to the 17p13.3 band. Separate evaluation was made for sectors corresponding to adenoma tissue with low-grade dysplasia, high-grade dysplasia, and early cancer. The same technique was also used in 20 cases of advanced adenocarcinoma of the large bowel. Loss of one centromeric signal was observed in 20, 40, 50, and 10% of low-grade dysplasia, high-grade dysplasia, early cancer, and advanced cancer, respectively (P<0.02 early vs. advanced cancer). Subtelomeric 17p deletions were seen in 60% of advanced cancer and in 15% of early cancer (P<0.01). These findings indicate that loss of genes from the 17p13.3 chromosome region may play an important role in sustaining the transition from early to advanced cancer in colorectal tumor progression.

Anti-tumor necrosis factor alpha monoclonal antibody (infliximab) for the treatment of Pyoderma gangrenosum associated with Crohn's disease.

Here we report a case of Pyoderma gangrenosum (PG) associated with Crohn's disease successfully treated with infliximab. The efficacy of this drug in many inflammatory diseases has already been reported, but its use in PG has only been seen in very few cases. Our study confirms that this therapy is a valid alternative solution for treating PG, which is often unresponsive to conventional therapies.

Germline APC mutation on the beta-catenin binding site is associated with a decreased apoptotic level in colorectal adenomas.

Germline mutations in APC tumor suppressor gene are responsible for familial adenomatous polyposis (FAP). A major role of these genetic changes is the constitutive activation of beta-catenin-Tcf-4 mediated transcription of nuclear target genes, but other cellular functions can be misregulated. To assess how different APC mutations can drive the early steps of colonic tumorigenesis, we studied the effect of 10 different germline-truncating alterations on the phenotype of the corresponding adenomas. A significant reduction of apoptosis, uncoupled with an increased c-myc and cyclin-D1 expression, was seen with a frameshift mutation on codon 1383, in the 20-aa repeats of the beta-catenin degradation domain, independent of a somatic alteration on the wild-type allele. The decreased apoptotic level was associated with a higher incidence of cancerization. No other APC mutation was linked with a similar effect, even in presence of a somatic allelic loss. These findings suggest that mutations in critical sites of the beta-catenin degradation domain of APC gene can convey a selective advantage to the colonic neoplastic clones by altering the apoptotic surveillance rather than enhancing the beta-catenin-Tcf-4 transcription of growth-promoting genes.

Baseline findings of the Italian multicenter randomized controlled trial of "once-only sigmoidoscopy"--SCORE.

BACKGROUND: A single sigmoidoscopy examination at around age 60 years has been proposed as a cost-effective strategy to prevent colorectal cancer. A multicenter randomized controlled trial, the SCORE trial, is in progress in Italy to estimate the impact of this strategy on colorectal cancer incidence and mortality and the duration of the protective effect. We present the baseline screening outcomes. METHODS: A questionnaire was mailed to a random sample of 236 568 people aged 55-64 years to assess their eligibility for and interest in screening. Those reporting a history of colorectal cancer, adenomas, inflammatory bowel disease, recent colorectal endoscopy, or two first-degree relatives with colorectal cancer were excluded. Eligible, interested respondents were assigned randomly to the control group (no further contact) or the intervention group (invitation to undergo sigmoidoscopy). Screenees with colorectal cancer, polyps larger than 5 mm, three or more adenomas, adenomas 5 mm or smaller with a villous component of more than 20%, or severe dysplasia were referred for colonoscopy. RESULTS: Of the 56 532 respondents (23.9% of those invited), 34 292 were enrolled and 17 148 were assigned to the screening group. Of those, 9999 attended and 9911 were actually examined by sigmoidoscopy. Distal adenomas were detected in 1070 subjects (10.8%). Proximal adenomas were detected in 116 of 747 (15.5%) subjects without cancer at sigmoidoscopy who then underwent colonoscopy. A total of 54 subjects was found to have colorectal cancer, a rate of 5.4 per 1000 (54% of which were Dukes' A). The procedures were relatively safe, with two perforations (one in 9911 sigmoidoscopy exams and one in 775 colonoscopies) and one hemorrhage requiring hospitalization after polypectomy during colonoscopy. The pain associated with sigmoidoscopy was described as mild or less than expected by 83.3% of the screenees. CONCLUSION: Sigmoidoscopy screening is generally acceptable to recipients and safe. The high yield of advanced adenomas is consistent with the projected impact of sigmoidoscopy screening on colorectal cancer incidence.