The Peptide Antibiotic Corramycin Adopts a ß-Hairpin-like Structure and Is Inactivated by the Kinase ComG.

The rapid development of antibiotic resistance, especially among difficult-to-treat Gram-negative bacteria, is recognized as a serious and urgent threat to public health. The detection and characterization of novel resistance mechanisms are essential to better predict the spread and evolution of antibiotic resistance. Corramycin is a novel and modified peptidic antibiotic with activity against several Gram-negative pathogens. We demonstrate that the kinase ComG, part of the corramycin biosynthetic gene cluster, phosphorylates and thereby inactivates corramycin, leading to the resistance of the host. Remarkably, we found that the closest structural homologues of ComG are aminoglycoside phosphotransferases; however, ComG shows no activity toward this class of antibiotics. The crystal structure of ComG in complex with corramycin reveals that corramycin adopts a ß-hairpin-like structure and allowed us to define the changes leading to a switch in substrate from sugar to peptide. Bioinformatic analyses suggest a limited occurrence of ComG-like proteins, which along with the absence of cross-resistance to clinically used drugs positions corramycin as an attractive antibiotic for further development.

Enterobacterales carrying chromosomal AmpC ß-lactamases in Europe (EuESCPM): Epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020-2022.

INTRODUCTION: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs. METHODS: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated. RESULTS: Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new ß-lactam/ß-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%). CONCLUSIONS: This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics.

Older Adult Woman in a Coma After Acute Laryngitis.

CASE PRESENTATION: A 72-year-old woman with a history of adenocarcinoma of the lung, for which she was receiving tyrosine kinase inhibitor therapy with osimertinib, was admitted to the ED because of clinical deterioration with extreme fatigue and fever. She was already receiving antibiotic therapy initiated by her general practitioner because of symptoms of an upper respiratory tract infection. She was febrile (38.5 °C) with normal laboratory values except for leukocytosis and elevated C-reactive protein. She was hospitalized because of profound general malaise. On the basis of the physician's working hypothesis of severe viral laryngitis, the antibiotic therapy was stopped, and only supportive measures were taken. Over the next 3 days, her condition deteriorated, and she developed respiratory symptoms with a right-sided pleural effusion demonstrated by ultrasound examination. Over time, the patient became increasingly confused and drowsy. There was preserved urinary output and a stable glomerular filtration rate of 57 mL/min. Further on, bilirubin levels as well as coagulation were normal, indicating the absence of any relevant underlying chronic liver condition. Clinically, there were no signs of meningitis. No sedative medications that would explain her confusion were given except for low-dose opioid analgesics. On day 4 after hospitalization, she was transferred to the shock room for immediate stabilization and diagnostics because of profound encephalopathy and increasing oxygen requirements.

Low neutrophil-to-lymphocyte ratio and pan-immune-inflammation-value predict nodal pathologic complete response in 1274 breast cancer patients treated with neoadjuvant chemotherapy: a multicenter analysis.

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51-0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44-0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)-/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12-0.83; p = 0.02) and ER-/HER2- (OR = 0.41; 95% CI, 0.17-0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806.

Energy-Constrained LOCC-Assisted Quantum Capacity of the Bosonic Dephasing Channel.

We study the LOCC-assisted quantum capacity of a bosonic dephasing channel with energy constraint on the input states. We start our analysis by focusing on the energy-constrained squashed entanglement of the channel, which is an upper bound for the energy-constrained LOCC-assisted quantum capacity. As computing energy-constrained squashed entanglement of the channel is challenging due to a double optimization (over the set of density matrices and the isometric extensions of a squashing channel), we first derive an upper bound for it, and then, we discuss how tight that bound is for the energy-constrained LOCC-assisted quantum capacity of the bosonic dephasing channel. In doling so, we prove that the optimal input state is diagonal in the Fock basis. Then, we analyze two explicit examples of squashing channels through which we derive explicit upper and lower bounds for the energy-constrained LOCC-assisted quantum capacity of the bosonic dephasing channel in terms of its quantum capacity with different noise parameters. As the difference between upper and lower bounds becomes smaller by increasing the dephasing parameter, the bounds become tighter.

QUIRMIA-A Phenotype-Based Algorithm for the Inference of Quinolone Resistance Mechanisms in Escherichia coli.

OBJECTIVES: Quinolone resistance in Escherichia coli occurs mainly as a result of mutations in the quinolone-resistance-determining regions of gyrA and parC, which encode the drugs' primary targets. Mutational alterations affecting drug permeability or efflux as well as plasmid-based resistance mechanisms can also contribute to resistance, albeit to a lesser extent. Simplifying and generalizing complex evolutionary trajectories, low-level resistance towards fluoroquinolones arises from a single mutation in gyrA, while clinical high-level resistance is associated with two mutations in gyrA plus one mutation in parC. Both low- and high-level resistance can be detected phenotypically using nalidixic acid and fluoroquinolones such as ciprofloxacin, respectively. The aim of this study was to develop a decision tree based on disc diffusion data and to define epidemiological cut-offs to infer resistance mechanisms and to predict clinical resistance in E. coli. This diagnostic algorithm should provide a coherent genotype/phenotype classification, which separates the wildtype from any non-wildtype and further differentiates within the non-wildtype. METHODS: Phenotypic susceptibility of 553 clinical E. coli isolates towards nalidixic acid, ciprofloxacin, norfloxacin and levofloxacin was determined by disc diffusion, and the genomes were sequenced. Based on epidemiological cut-offs, we developed a QUInolone Resistance Mechanisms Inference Algorithm (QUIRMIA) to infer the underlying resistance mechanisms responsible for the corresponding phenotypes, resulting in the categorization as "susceptible" (wildtype), "low-level resistance" (non-wildtype) and "high-level resistance" (non-wildtype). The congruence of phenotypes and whole genome sequencing (WGS)-derived genotypes was then assigned using QUIRMIA- and EUCAST-based AST interpretation. RESULTS: QUIRMIA-based inference of resistance mechanisms and sequencing data were highly congruent (542/553, 98%). In contrast, EUCAST-based classification with its binary classification into "susceptible" and "resistant" isolates failed to recognize and properly categorize low-level resistant isolates. CONCLUSIONS: QUIRMIA provides a coherent genotype/phenotype categorization and may be integrated in the EUCAST expert rule set, thereby enabling reliable detection of low-level resistant isolates, which may help to better predict outcome and to prevent the emergence of clinical resistance.

Comparison of Disk Diffusion, E-Test, and Broth Microdilution Methods for Testing In Vitro Activity of Cefiderocol in Acinetobacter baumannii.

The reference method for cefiderocol antimicrobial susceptibility testing is broth microdilution (BMD) with iron-depleted-Mueller-Hinton (ID-MH) medium, whereas breakpoints recommended for disk diffusion (DD) are based on MH-agar plates. We aimed to compare the performance of the commercial BMD tests ComASP (Liofilchem) and UMIC (Bruker), and DD and E-test using MH- and ID-MH-agar plates with the reference BMD method using 100 carbapenem-resistant-A. baumannii isolates. Standard BMD was performed according to the EUCAST guidelines; DD and E-test were carried out using two commercial MH-agar plates (BioMérieux and Liofilchem) and an in-house ID-MH-agar plate, while ComASP and UMIC were performed according to the manufacturer's guidelines. DD performed with the ID-MH-agar plates led to a higher categorical agreement (CA, 95.1%) with standard BMD and fewer categorization errors compared to the commercial MH-agar plates (CA BioMérieux 91.1%, Liofilchem 89.2%). E-test on ID-MH-agar plates exhibited a significantly higher essential agreement (EA, 75%) with standard BMD compared to the two MH-agar plates (EA BioMérieux 57%, Liofilchem 44%), and showed a higher performance in detecting high-level resistance than ComASP and UMIC (mean log2 difference with standard BMD for resistant isolates of 0.5, 2.83, and 2.08, respectively). In conclusion, DD and E-test on ID-MH-agar plates exhibit a higher diagnostic performance than on MH-agar plates and the commercial BMD methods. Therefore, we recommend using ID-MH-agar plates for cefiderocol susceptibility testing of A. baumannii.

Stabilizer codes for open quantum systems.

The Lindblad master equation describes the evolution of a large variety of open quantum systems. An important property of some open quantum systems is the existence of decoherence-free subspaces. A quantum state from a decoherence-free subspace will evolve unitarily. However, there is no procedural and optimal method for constructing a decoherence-free subspace. In this paper, we develop tools for constructing decoherence-free stabilizer codes for open quantum systems governed by the Lindblad master equation. This is done by pursuing an extension of the stabilizer formalism beyond the celebrated group structure of Pauli error operators. We then show how to utilize decoherence-free stabilizer codes in quantum metrology in order to attain the Heisenberg limit scaling with low computational complexity.

Risk of ileocolic anastomosis failure after right hemicolectomy for cancer. A comparison between different techniques.

BACKGROUND: In recent years, the role of laparoscopic approach in the surgical treatment of right colon cancer has increased. Results comparing the different techniques of ileocolic anastomoses are controversial, with studies only reporting some advantages of the intracorporeal laparoscopic technique. The aim of this study is to compare the outcomes between laparoscopic versus open hemicolectomy for right colon cancer, focusing on anastomotic techniques (intracorporeal vs extracorporeal in the laparoscopic procedure, and manual vs mechanical in the laparotomic procedure). METHODS: This is a retrospective single center study enrolling patients with right colon cancer from January 2016 to December 2020. Primary endpoint of the study was the rate of anastomotic leak (AL). RESULTS: A total of 161 patients who underwent right hemicolectomy were enrolled: 91 were performed with laparoscopic technique, and 70 with open technique. Overall, AL occurred in 15 pts (9.3%). We observed 4 AL in intracorporeal (12.9%) and 6 in extracorporeal (10%) anastomoses, respectively. In the laparotomy group 5 patients (7.1%) developed AL, of which 3 (5.7%) and 2 (11.1%) manually and mechanically performed, respectively. CONCLUSIONS: Based on our findings, laparoscopic hemicolectomy has a higher incidence of anastomotic leak. In the laparoscopic group, we observed the lowest rate of AL with extracorporeal mechanical anastomosis. When performed extracorporeally with open technique, hand-sewn anastomosis has better results than mechanical. KEY WORDS: Anastomosis, Cancer, Ileotransverse, Leakage, Right Colectomy.

Detection of Extended-Spectrum ß-Lactamases (ESBLs) and AmpC in Class A and Class B Carbapenemase-Producing Enterobacterales.

In carbapenemase-producing Enterobacterales (CPE) additional ß-lactam resistance mechanisms such as extended-spectrum-ß-lactamases (ESBL) and/or AmpC-ß-lactamases are generally difficult to detect by phenotypical methods. Recently, a modified version of the CLSI ESBL confirmatory combination disc diffusion (CDD) test, which involves the addition of boronic acid and EDTA on discs containing ESBL and AmpC substrates ± inhibitors, has been proposed for the detection of ESBL in class A and class B CPE. Here, the performance of the modified CDD test was evaluated using 121 genotypically characterized class A and class B CPE. Also, the effectiveness of the NG-Test CTX-M-MULTI lateral flow immunoassay was evaluated for ESBL detection. For class A CPE (n = 47), the modified CDD method exhibited an equal specificity (95.7%) and a higher sensitivity (100%) compared to the standard method (91.7%). The CTX-M-MULTI test detected ESBL in all CTX-M-type ESBL producers (n = 23), whereas it was negative for all CTX-M-type ESBL-negative isolates (n = 24). For class B CPE (n = 71), the modified method significantly improved both sensitivity (95%) and specificity (100%) in detecting ESBL compared to the standard method (17.5% sensitivity and 83.9% specificity). In comparison, the CTX-M-MULTI led to identification of ESBL in all CTX-M-ESBL-producers (n = 39) and no false-positive signal was generated with the CTX-M-type-ESBL-negative isolates (n = 30). Furthermore, the modified CDD improved the robustness of the method for AmpC detection (inconclusive results were produced in 53/57 and 10/57 cases with the standard and modified method, respectively), although the sensitivity of the test was poor (23.5%). Here, we propose a practical and cost-effective approach combining the modified CDD and the CTX-M-MULTI test for detection of ESBL and/or AmpC in class A and B CPE. IMPORTANCE Antimicrobial resistance is a growing public health threat of broad concern worldwide. Timely detection of antibiotic resistance mechanisms can help to monitor and to curb the spread of resistant bacteria within the hospital setting as well as in the environment. In this work we report an accurate and affordable method to phenotypically identify difficult-to-detect resistance determinants in highly resistant (carbapenemase-producing) bacteria. This method may be implemented in any diagnostic microbiology lab and may reduce the underreporting of relevant resistance mechanisms.

Impact of the COVID-19 Pandemic on Enhanced Recovery After Surgery (ERAS) Application and Outcomes: Analysis in the "Lazio Network" Database.

BACKGROUND: The aim of this study was to investigate how the COVID-19 pandemic influenced ERAS program application in colorectal surgery across hospitals in the Lazio region (central district in Italy) participating in the "Lazio Network" project. METHODS: A multi-institutional database was constructed. All patients included in this study underwent elective colorectal surgery for both malignant and benign disease between January 2019 and December 2020. Emergency procedures were excluded. The population was divided into 2 groups: a pre-COVID-19 group (PG) of patients operated on between February and December 2019 and a COVID-19 group (CG) of patients operated on between February and December 2020, during the first 2 waves of the pandemic in Italy. RESULTS: The groups included 622 patients in the PG and 615 in the CG treated in 8 hospitals of the network. The mean number of items applied was higher in the PG (65.6% vs. 56.6%, p < 0.001) in terms of preoperative items (64.2% vs. 50.7%, p < 0.001), intraoperative items (65.0% vs. 53.3%, p < 0.001), and postoperative items (68.8% vs. 63.2%, p < 0.001). Postoperative recovery was faster in the PG, with a shorter time to first flatus, first stool, autonomous mobilization and discharge (6.82 days vs. 7.43 days, p = 0.021). Postoperative complications, mortality and reoperations were similar among the groups. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the application of ERAS in the centers of the "Lazio Network" study group, with a reduction in adherence to the ERAS protocol in terms of preoperative, intraoperative and postoperative items. In addition, in the CG, the patients had worse postoperative outcomes with respect to recovery and discharge.

Gender differences in Anxious-depressive symptomatology, Metabolic Syndrome and Colorectal Adenomas among outpatients undergoing colonoscopy: a cross-sectional study according to a PNEI perspective.

BACKGROUND AND AIM OF THE WORK: To explore gender differences in patients suffering from anxious-depressive symptoms, Metabolic Syndrome (MetS) and Colorectal Adenomas (CRAs) in a sample of outpatients undergoing colonoscopy for screening purposes. METHODS: Cross-sectional study. 126 consecutive outpatients of both sexes undergoing colonoscopy for non-specific abdominal symptoms between January 2015 and June 2021 at the Modena Policlinico General Hospital (Modena, Northern Italy) were enrolled. MetS was diagnosed according to ATPIII and IDF criteria. Anxiety and depression were assessed with the Hospital Anxiety and Depression Scale (HADS), while the Temperament and Character Inventory (TCI) was used to study personality. The SF-36 was also included as a measure of quality of life perception. RESULTS: Among 126 outpatients (51.60% male) undergoing colonoscopy, 51 (44%) had CRAs, 54 (47%) MetS, 41 (41.40%) anxiety symptoms, 22 (22.20%) depressive symptoms and 13 (13.10%) combined anxious-depressive symptoms. HADS-Anxiety (t=2.68, p=0.01) and TCI Reward Dependence (TCI-RD) (t=3.01, p=0.00) mean scores were significantly higher in women; conversely, SF-36 Mental Component Summary scores were higher in men. CRAs were significantly prevalent in men (χ2=9.32, p=0.00) and were statistically significantly associated with male sex at the univariate logistic regression analysis (OR=3.27; p<0.01). At the multivariate logistic regression, diastolic hypertension (p<0.01) was positively associated with male sex, while TCI-RD (p=0.04) and HDL hypocholesterolemia (p=0.02) were inversely associated with male sex. CONCLUSIONS: Several significant gender differences in anxious-depressive symptoms, MetS and CRAs were found. These preliminary data suggest the need to consider gender specificities while implementing therapeutic, diagnostic, and preventive strategies.

Enhanced recovery after surgery (ERAS) program in octogenarian patients: a propensity score matching analysis on the "Lazio Network" database.

PURPOSE: The aim of this study was to evaluate the safety and compliance with the enhanced recovery after surgery (ERAS) protocol in octogenarian patients undergoing colorectal surgery in 12 Italian high-volume centers. METHODS: A retrospective analysis was conducted in a consecutive series of patients who underwent elective colorectal surgery between 2016 and 2018. Patients were grouped by age (≥ 80 years vs < 80 years), propensity score matching (PSM) analysis was performed, and the groups were compared regarding clinical outcomes and the mean number of ERAS items applied. RESULTS: Out of 1646 patients identified, 310 were octogenarians. PSM identified 2 cohorts of 125 patients for the comparison of postoperative outcomes and ERAS compliance. The 2 groups were homogeneous regarding the clinical variables and mean number of ERAS items applied (11.3 vs 11.9, p-ns); however, the application of intraoperative items was greater in nonelderly patients (p 0.004). The functional recovery was similar between the two groups, as were the rates of postoperative severe complications and 30-day mortality rate. Elderly patients had more overall complications. Furthermore, the mean hospital stay was higher in the elderly group (p 0.027). Multivariable analyses documented that postoperative stay was inversely correlated with the number of ERAS items applied (p < 0.0001), whereas age ≥ 80 years significantly correlated with the overall complication rate (p 0.0419). CONCLUSION: The ERAS protocol is safe in octogenarian patients, with similar levels of compliance and surgical outcomes. However, octogenarian patients have a higher rate of overall complications and a longer hospital stay than do younger patients.

Myelodysplastic Syndromes with Isolated 20q Deletion: A New Clinical-Biological Entity?

Aims: To define the peculiar features of patients with the deletion of the chromosome 20 long arm (del20q), data from 69 patients with myelodysplastic syndromes (MDSs) and isolated del20q, followed by the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L) and Ospedale Torrette of Ancona, were collected and compared with those of 502 MDS patients with normal karyotype (NK-MDS). Results: Compared to the NK-MDS group, patients with del20q at diagnosis were older (p = 0.020) and mainly male (p = 0.006). They also had a higher rate of bone marrow blast < 5% (p = 0.004), a higher proportion of low and int-1 risk according to IPSS score (p = 0.023), and lower median platelet (PLT) count (p < 0.001). To date, in the del20q cohort, 21 patients (30.4%) received no treatment, 42 (61.0%) were treated with erythropoiesis-stimulating agents (ESA), 3 (4.3%) with hypomethylating agents, and 3 (4.3%) with other treatments. Among 34 patients evaluable for response to ESA, 21 (61.7%) achieved stable erythroid response according to IWG 2006 criteria and 13 (38.2%) were resistant. Nine patients (13.0%) progressed to acute myeloid leukaemia (AML) after a median time from diagnosis of 28 months (IR 4.1−51.7). The median overall survival (OS) of the entire cohort was 60.6 months (95% CI 54.7−66.4). the 5-year cumulative OS was 55.9% (95% CI 40.6−71.2). Conclusion: According to our results, we hypothesize that MDSs with isolated del 20q may represent a distinct biological entity, with peculiar clinical and prognostic features. The physio-pathological mechanisms underlying the deletion of the chromosome 20 long arm are still unclear and warrant future molecular analysis.

Expression of Autophagic and Inflammatory Markers in Normal Mucosa of Individuals with Colorectal Adenomas: A Cross Sectional Study among Italian Outpatients Undergoing Colonoscopy.

Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in Western industrialized countries. Lifetime risk of colorectal cancer may reach 6% of the population living in developed countries. In the current era of personalized medicine, CRC is no longer considered as a single entity. In more recent years many studies have described the distinct differences in epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and outcome depending on the anatomical site. The aim of our study is to assess in a multidimensional model the association between metabolic status and inflammatory and autophagic changes in the normal colorectal mucosa classified as right-sided, left-sided and rectum, and the presence of adenomas. One hundred and sixteen patients undergoing colonoscopy were recruited and underwent a complete serum lipid profile, immunofluorescence analysis of colonic biopsies for MAPLC3 and myeloperoxidase expression, matched with clinical and anthropometric characteristics. Presence of adenomas correlated with cholesterol (total and LDL) levels, IL-6 levels, and MAPLC3 tissue expression, especially in the right colon. In conclusion, serum IL-6 amount and autophagic markers could be good predictors of the presence of colorectal adenomas.

Antimicrobial susceptibility testing is crucial when treating Finegoldia magna infections.

Finegoldia magna is an anaerobic gram-positive bacterium that can cause invasive human infections. Recently, a 52-year-old patient suffering from a periprosthetic joint infection (PJI) due to F. magna was treated with cefepime on hemodialysis; however, treatment failed due to relapse caused by antibiotic-resistant strains. Reports on the antimicrobial susceptibility of F. magna clinical isolates are rare. We collected 57 clinical F. magna isolates from Zurich, Switzerland, between September 2019 and July 2020 and tested their antimicrobial susceptibility to investigate the local resistance pattern. Antimicrobial susceptibility testing (AST) was evaluated for nine antibiotics (benzylpenicillin, amoxicillin/clavulanic acid, cefuroxime, cefepime, levofloxacin, rifampicin, metronidazole, doxycycline, and clindamycin) by E-test according to CLSI guidelines. All F. magna strains were susceptible to benzylpenicillin, amoxicillin/clavulanic acid, and metronidazole, while 75% to clindamycin. F. magna isolates showed MIC values lower than species-unrelated breakpoints for cefuroxime, levofloxacin, and cefepime in 93%, 56%, and 32% of the cases, respectively. MIC values for rifampicin and doxycycline were lower than locally determined ECOFFs in 98% and 72% of the cases, respectively. In summary, we recommend the use of benzylpenicillin, amoxicillin/clavulanic acid, or metronidazole without prior AST as first-line treatment option against F. magna PJI infections. If cefuroxime, cefepime, levofloxacin, rifampicin, doxycycline, or clindamycin are used, AST is mandatory.

Entanglement-Assisted Quantum Codes from Cyclic Codes.

Entanglement-assisted quantum-error-correcting (EAQEC) codes are quantum codes which use entanglement as a resource. These codes can provide better error correction than the (entanglement unassisted) codes derived from the traditional stabilizer formalism. In this paper, we provide a general method to construct EAQEC codes from cyclic codes. Afterwards, the method is applied to Reed-Solomon codes, BCH codes, and general cyclic codes. We use the Euclidean and Hermitian construction of EAQEC codes. Three families have been created: two families of EAQEC codes are maximal distance separable (MDS), and one is almost MDS or almost near MDS. The comparison of the codes in this paper is mostly based on the quantum Singleton bound.

A p-Adic Model of Quantum States and the p-Adic Qubit.

We propose a model of a quantum N-dimensional system (quNit) based on a quadratic extension of the non-Archimedean field of p-adic numbers. As in the standard complex setting, states and observables of a p-adic quantum system are implemented by suitable linear operators in a p-adic Hilbert space. In particular, owing to the distinguishing features of p-adic probability theory, the states of an N-dimensional p-adic quantum system are implemented by p-adic statistical operators, i.e., trace-one selfadjoint operators in the carrier Hilbert space. Accordingly, we introduce the notion of selfadjoint-operator-valued measure (SOVM)-a suitable p-adic counterpart of a POVM in a complex Hilbert space-as a convenient mathematical tool describing the physical observables of a p-adic quantum system. Eventually, we focus on the special case where N=2, thus providing a description of p-adic qubit states and 2-dimensional SOVMs. The analogies-but also the non-trivial differences-with respect to the qubit states of standard quantum mechanics are then analyzed.

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients.

BACKGROUND: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. PATIENTS AND METHODS: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). RESULTS: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. CONCLUSION: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.