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Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

Cognitive impairment (CI) is a frequent and disabling symptom in Multiple Sclerosis (MS). Axonal damage may contribute to CI development from early stages. Nevertheless, no biomarkers are at the moment available to track CI in MS patients. We aimed to explore the correlation of cerebrospinal fluid (CSF) axonal biomarkers, in particular: light-chain neurofilaments (NFL), Tau, and Beta-amyloid protein (Abeta) in MS patients with CI at the diagnosis. 62 newly diagnosed MS patients were enrolled, and cognition was evaluated using the Brief International Cognitive Assessment for MS (BICAMS) battery. CSF NFL, Abeta, and Tau levels were determined with commercial ELISA. Patients with CI (45.1%) did not differ for demographic, clinical, and MRI characteristics (except for lower educational level), but they displayed greater neurodegeneration, exhibiting higher mean CSF Tau protein (162.1 ± 52.96 pg/ml versus 132.2 ± 63.86 pg/ml p:0.03). No differences were observed for Abeta and NFL. The number of impaired tests and Tau were significantly correlated (r:0.32 p:0.01). Tau was higher in particular in patients with slowed information processing speed (IPS) (p:0.006) and a linear regression analysis accounting for EDSS, MRI, and MS subtype confirmed Tau as a weak predictor of IPS and cognitive impairment. In conclusion, CI has an important burden on the quality of life of MS patients and should be looked for even at diagnosis. Axonal damage biomarkers, and in particular Tau, seem to reflect cognition impairment in the early stages.

Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.

Introduction: Multiple Sclerosis (MS) is a chronic autoimmune disease, displaying inflammation and neurodegeneration as neuropathological hallmarks. Nonetheless, the exact mechanisms underlying axonal and neuronal loss remain unclear. Several biomarkers have been investigated, with serum neurofilaments light chain (NFLs) being the most promising. Cerebrospinal fluid (CSF) levels of Tau and Beta-amyloid (Abeta) are currently used as biomarkers in other neurodegenerative diseases. Conversely in MS, investigation of CSF Tau and Abeta levels so far were reported to provide information on disease prognosis, but these results have not been replicated. Aim of this work was to assess whether CSF Tau and Abeta levels could predict early disability accumulation in MS patients at diagnosis. Methods: 100 MS patients underwent CSF analysis during their diagnostic work-up. Demographic, clinical, radiological features, and CSF were collected at baseline. MS severity score (MSSS) and age-related MSSS (ARMSS) were calculated at last follow-up. Statistical analysis was performed with the Mann–Whitney test for comparisons between groups, Spearman’s coefficient and multiple regression analysis for significant predictors.Results: Baseline CSF Tau levels correlated with MSSS (p=0.0001) and ARMSS (p=0.0176) after a mean two years follow-up. Predictors of early disability evaluated with MSSS and ARMSS were CSF Tau (p=0.009 and p=0.01), spinal cord involvement (p=0.029 and p=0.008), age at MS diagnosis (p=0.001), and high brain lesion load (p=0.02) at baseline. Conclusion: CSF Tau levels showed a predictive value comparable to MRI features and age at diagnosis. We hypothesize that CSF Tau levels express chronic axonal damage, contributing to early MS disability.

Cerebrospinal fluid (CSF) kappa free light chain (KFLC) index has been described as a reliable marker of intrathecal IgG synthesis to diagnose multiple sclerosis (MS). Our aims were: (1) to compare the efficiency of KFLC through different interpretation approaches in diagnosing MS. (2) to evaluate the prognostic value of KFLC in radiologically and clinically isolated syndromes (RIS-CIS). We enrolled 133 MS patients and 240 with other neurological diseases (93 inflammatory including 18 RIS-CIS, 147 non-inflammatory). Albumin, lambda free light chain (LFLC) and KFLC were measured in the CSF and serum by nephelometry. We included two groups of markers: (a) corrected for blood-CSF barrier permeability: immunoglobulin G (IgG), KFLC and LFLC indexes. (b) CSF ratios (not including albumin and serum-correction): CSF KFLC/LFLC, CSF KFLC/IgG, CSF LFLC/IgG. KFLC were significantly higher in MS patients compared to those with other diseases (both inflammatory or not). KFLC index and CSF KFLC/IgG ratio showed high sensitivity (93% and 86.5%) and moderate specificity (85% and 88%) in diagnosing MS. RIS-CIS patients who converted to MS showed greater KFLC index and CSF KFLC/IgG. Despite OB are confirmed to be the gold-standard to detect intrathecal IgG synthesis, the KFLC confirmed their accuracy in MS diagnosis. A “kappa-oriented” response characterizes MS and has a prognostic impact in the RIS-CIS population.

Background: Kidney function in preterm newborns may be impaired by many factors. Methods: 71 newborns with gestational age (GA) &lt, 32 weeks were enrolled. Serum creatinine (sCr), cystatin C (CysC), beta-trace protein (BTP) and urea were measured at T0 (3rd day of life) and T36 (GA 36 weeks), and estimated glomerular filtration rate (eGFR) was calculated according to different formulas at T36. Pre-natal and post-natal kidney injury risk scores were calculated. Results: Newborns with GA &le, 28 weeks had higher sCr at T0, and lower sCr, BTP and higher urea levels at T36 (p = 0.007, p = 0.005 and p = 0.029, respectively). eGFR values were not different according to GA when calculated by the formulas using only CysC, but were higher in subjects with GA &le, 28 weeks according to the other formulas. The post-natal score was positively correlated with eGFR according to sCr-based formulas, but the correlations did not persist when adjusted for urea levels and GA. Conclusions: CysC-based eGFR values are not influenced by GA. Post-natal score shows a direct correlation with eGFR according to sCr-based formulas, not persisting after adjustment for GA and urea levels, implying the importance of the nutritional status, since more premature subjects receive a more aggressive nutritional regimen, testified by higher urea levels.

Introduction Axonal loss is an important feature of Multiple Sclerosis (MS), being strongly related to irreversible disability accumulation. Nonetheless, the exact mechanisms underlying axonal loss remain unclear. Cerebrospinal fluid (CSF) levels of Tau and Beta-amyloid (Abeta) currently represent diagnostic biomarkers in other neurodegenerative diseases. In MS, studies on CSF Tau and Abeta provided preliminary informations on disease prognosis, but results have not yet been replicated. Methods We investigated whether CSF Tau and Abeta levels could predict early disability accumulation in MS patients. 100 patients underwent CSF analysis during their diagnostic work-up. Demographic, clinical, radiological features and CSF were collected at baseline. MS severity score (MSSS) and age-related MSSS (ARMSS) were calculated at last follow-up. We performed Mann–Whitney test, Spearman's coefficient, and multiple regression analysis for significant predictors of disability based on CSF Abeta and Tau levels, gender, age at diagnosis and MRI characteristics at baseline. Results Baseline CSF Tau levels moderately correlated with MSSS (r=0.372 p=0.0001) and weakly with ARMSS (r=0.237 p=0.0176) after a mean two years follow-up. Predictors of early disability evaluated with MSSS and ARMSS were CSF Tau (Beta:0.258 p=0.009 and Beta:0.252 p=0.01) and spinal cord involvement (Beta:0.196 p=0.029 and Beta:0.240 p=0.008); as well as age at MS diagnosis (Beta:0.286 p=0.001) for MSSS, and high brain lesion load (Beta:0.207 p=0.02) for ARMSS. Conclusion CSF Tau levels at diagnosis possibly has a predictive value along with MRI features and age at diagnosis. We hypothesize that Tau levels may express chronic axonal damage, possibly contributing to early MS disability.

The K free light chain (K) index has been suggested as a reliable marker of intrathecal synthesis,despite the 2017 McDonald criteria for multiple sclerosis (MS) suggesting to &ldquo, interpret with caution positiveimmunoglobulin G (IgG) index when testing for oligoclonal bands (OB) is negative or not performed&rdquo, Theaim of this study was to compare the performance of K and IgG indexes for MS diagnosis and OB detectionin a cohort of Italian patients. We enrolled 385 patients (127 MS, 258 non-MS) who had cerebrospinal fluid(CSF) analysis, including isoelectric focusing (IEF), to detect OB in the diagnostic work-up. Albumin, IgGand free light chains were measured by nephelometry and used to calculate IgG and K indexes. Althoughthe two markers were highly related (r = 0.75, r2 = 0.55, p &lt, 0.0001), the K index showed greater sensitivity andnegative predictive value (versus the IgG index) for OB detection (97% versus 48% and 97% versus 71%) andMS diagnosis (96% versus 50% and 98% versus 78%). These results support K index (and not IgG index) as afirst-line marker for MS, followed by IEF, according to a sequential testing approach in CSF analysis.

Background Isoelectrofocusing (IEF) to detect oligoclonal bands (OBCs) in cerebrospinal fluid (CSF) is the gold standard approach for evaluating intrathecal immunoglobulin synthesis in multiple sclerosis (MS) but the kappa free light chain index (KFLCi) is emerging as an alternative marker, and the combined/sequential uses of IEF and KFLCi have never been challenged. Methods CSF and serum albumin, IgG, kFLC and lFLC were measured by nephelometry; albumin, IgG and kFLC quotients as well as Link and kFLC indexes were calculated; OCBs were evaluated by immunofixation. A total of 150 consecutive patients: 48 with MS, 32 with other neurological inflammatory diseases (NID), 62 with neurological non-inflammatory diseases (NNID), and 8 without any detectable neurological disease (NND) were investigated. Results Both IEF and KFLCi showed a similar accuracy as diagnostic tests for multiple sclerosis. The high sensitivity and specificity associated with the lower cost of KFLCi suggested to use this test first, followed by IEF as a confirmative procedure. The sequential use of IEF and KFLCi showed high diagnostic efficiency with cost reduction of 43 and 21%, if compared to the contemporary use of both tests, or the unique use of IEF in all patients. Conclusions The "sequential testing" using KFLCi followed by IEF in MS represents an optimal procedure with accurate performance and lower costs.

From June 2004 to June 2005, a total of 58 mycobacterial isolates were recovered from inpatients admitted to the “Ospedale Maggiore” in Novara, Italy. Most of the above strains were from respiratory secretions. Among the 32 isolates identified as Mycobacterium tuberculosis complex (MTC), susceptibility testing to streptomycin, isoniazid, rifampin, ethambutol and pyrazinamide was subsequently performed by using the MGIT 960 system. Starting from positive cultures, the Genotype MTBDR “Arnika” test, based on target amplification and stripbased reverse hybridization was also carried out. In addition to the MTC identification, the test can investigate the resistance to both rifampin (by molecular analysis of the rpoB region) and isoniazid (by detecting mutations at the resistance domain of katG gene). The results were compared with those obtained by conventional liquid medium susceptibility testing. Full agreement with both drugs was obtained on all the tested isolates. In conclusion, the GenoType MTBDR assay was found to enable a very rapid resistance detection of the most important anti-tubercular drugs.These data are important to set up an effective therapy and consequent disease control.

Central venous catheter represents a major source of nosocomial bloodstream infection, which cause considerable excess morbidity.The diagnosis of catheter-related infections relies on the presence of clinical manifestation of infection and the evidence of colonization of the catheter tip by bacteria or fungi. The most frequent pathogens were Gram-positive organisms, mainly coagulase negative staphylococci, followed by Gram-negative and mycetes. During the years 2001-2003 we examined 2079 vascular catheters, of which 896 were positive for bacterial and fungal species. Of these, 675 (75,3%) involved Gram-positive bacterial, 145 (16,2%) Gram-negative and 76 (8,5%) mycetes.

In thIe latter years Enterobacter cloacae has been counted as a very important occasional pathogen, above all in causing hospital infections.The micro-organism’s interesting increases because of its high resistance in vitro to many antimicrobial agents. For this reason it would be possible to find out others resistance mutant phenotypes. The results (2000-2001 and the first six months of 2002), carried out 341 isolated samples from hospital patients, show that the percentage of these E. cloacae is little more than 1%, increasing prevalence of patients belonging to General Surgery and Intensive Care Unit. The susceptible tests suggest (without important differences during the whole year) that most of the clinical isolates have moderate or high level resistance to various antimicrobial agents (penicillins, cephalosporins, aminoglycosides, quinolones, monobactam) and almost all were susceptible to amikacin, carbapenems (imipenem) and trimethoprim/sulfmamethoxazolo. Always regarding the resistance of these pathogens, it was possible to find out some phenotypes, and one of these, among 172 isolates belonging to Intensive Care Unit, was a particular multiresistance phenotype. The VITEK ESsL detection test and the conventional double disk synergy test for detection of ESsL find out some phenotypes showing expression of stably derepressed beta-lactamase.