Linear regression models and k-means clustering for statistical analysis of fNIRS data

We propose a new algorithm, based on a linear regression model, to statistically estimate the hemodynamic activations in fNIRS data sets. The main concern guiding the algorithm development was the minimization of assumptions and approximations made on the data set for the application of statistical tests. Further, we propose a K-means method to cluster fNIRS data (i.e. channels) as activated or not activated. The methods were validated both on simulated and in vivo fNIRS data. A time domain (TD) fNIRS technique was preferred because of its high performances in discriminating cortical activation and superficial physiological changes. However, the proposed method is also applicable to continuous wave or frequency domain fNIRS data sets

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis.

Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to their potential for altering the functional and anatomical integrity of the peritoneal membrane. Many of these effects are thought to be due to the high glucose content of these solutions, with attendant issues of products generated during heat treatment of glucose-containing solutions. Moreover, excessive intraperitoneal absorption of glucose from the dialysate has many potential systemic metabolic effects. This article reviews the efforts to develop alternative PD solutions that obviate some of these side effects, through the replacement of part of their glucose content with other osmolytes which are at least as efficient in removing fluids as glucose, but less impactful on patient metabolism. In particular, we will summarize clinical studies on the use of alternative osmotic ingredients that are commercially available (icodextrin and amino acids) and preclinical studies on alternative solutions under development (taurine, polyglycerol, carnitine and xylitol). In addition to the expected benefit of a glucose-sparing approach, we describe an 'osmo-metabolic' approach in formulating novel PD solutions, in which there is the possibility of exploiting the pharmaco-metabolic properties of some of the osmolytes to attenuate the systemic side effects due to glucose. This approach has the potential to ameliorate pre-existing co-morbidities, including insulin resistance and type-2 diabetes, which have a high prevalence in the dialysis population, including in PD patients

Complete Nucleotide Sequence of Plasmids of Two Escherichia coli Strains Carrying blaNDM–5 and blaNDM–5 and blaOXA–181 From the Same Patient

Aim of this study was to genetically characterize two carbapenemase-producing Escherichia coli strains obtained from a pediatric patient affected by diarrhea, expressing OXA-181 and/or NDM-5 type enzymes. The above microorganisms were collected in the same Desenzano hospital (Northern Italy) where the blaNDM–5 gene was detected for the first time in Italy 3 years ago. One strain (5P), belonged to sequence type ST405/ST477 (according to Pasture/Oxford schemes) and serotype O102:H6. It was characterized by a 130562 bp multi-replicon plasmid IncFII/IncFIA/IncFIB (pVSI_NDM-5) enclosing two main antibiotic resistance islands: (i) ARI-I, 10030 bp in size, carried genes coding for β-lactam- (blaOXA–1, blaCTX–M–15), fluoroquinolone/aminoglycoside- (aac(6′)-lb-cr) and phenicol- resistance (catB3), (ii) ARI-II, 15326 bp in size, carried genes coding for sulfonamide- (sul1), β-lactam- (blaNDM–5, blaTEM–1B), phenicol- (catB3), trimethoprim- (dfrA17), antiseptic- (qacEΔ1), and aminoglycoside- (aadA5, rmtB) resistance. The other isolate (5M), belonged to sequence type ST2659/ST759 and serotype O50/02:H18, and carried four plasmids: a 153866 bp multi-replicon IncFII/IncFIA/IncFIB (pISV_IncFII_NDM-5), an 89866 bp IncI1 plasmid, a 51480 bp IncX3 plasmid (pISV_IncX3_OXA181), and a 41143 bp IncI plasmid (pISV_IncI_CMY-42). pISV_IncFII_NDM-5 carried two main antibiotic resistance islands: (i) ARI-III, 12220 bp in size, carried genes coding for β-lactam- (blaOXA–1), fluoroquinolone/aminoglycoside- (aac(6′)-lb-cr), tetracycline- (tet(B)) and phenicol- resistance (catB3, catA1), and ii) ARI-IV, 26527 bp in size, carried determinants coding for macrolide- (erm(B), mph(A)), sulfonamide- (sul1), beta-lactam- (blaNDM–5, blaTEM–1B), trimethoprim- (dfrA14, dfrA12), antiseptic- (qacEΔ1), and aminoglycoside- resistance (aadA5). pISV_IncI_CMY-42 harbored the blaCMY–42 gene coding for beta-lactam resistance, pISV_IncX3_OXA181 harbored genes encoding fluoroquinolone- (qnrS1) and beta-lactams- resistance (blaOXA–181). In conclusion, the detection of two different NDM-5 E. coli strains from a pediatric patient with a history of travel to the Far East countries strongly highlight an increasing trend and risk of importation from such areas

Impact of the rs1024611 polymorphism of ccl2 on the pathophysiology and outcome of primary myelofibrosis

Single nucleotide polymorphisms (SNPs) can modify the individual pro-inflammatory background and may therefore have relevant implications in the MPN setting, typified by aberrant cytokine production. In a cohort of 773 primary myelofibrosis (PMF), we determined the contribution of the rs1024611 SNP of CCL2—one of the most potent immunomodulatory chemokines—to the clinical and biological characteristics of the disease, demonstrating that male subjects carrying the homozygous genotype G/G had an increased risk of PMF and that, among PMF patients, the G/G genotype is an independent prognostic factor for reduced overall survival. Functional characterization of the SNP and the CCL2-CCR2 axis in PMF showed that i) homozygous PMF cells are the highest chemokine producers as compared to the other genotypes; ii) PMF CD34+ cells are a selective target of CCL2, since they uniquely express CCR2 (CCL2 receptor); iii) activation of the CCL2-CCR2 axis boosts pro-survival signals induced by driver mutations via Akt phosphorylation; iv) ruxolitinib effectively counteracts CCL2 production and down-regulates CCR2 expression in PMF cells. In conclusion, the identification of the role of the CCL2/CCR2 chemokine system in PMF adds a novel element to the pathophysiological picture of the disease, with clinical and therapeutic implications

Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results

n/

HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients

The deregulation of the homeobox genes as homeoboxB (HOXB)-7 has been previously associated to tumor progression and angiogenesis; here we investigated the potential role of HOXB7 in the pro-angiogenic properties of multiple myeloma (MM) cells. We found that HOXB7 was expressed in 10 out of 22 MM patients analyzed at the diagnosis related to high bone marrow angiogenesis and overexpressed in about 40% of myeloma cell lines compared with normal plasma cells. Enforced HOXB7 expression in MM cells by a lentiviral vector significantly modified their transcriptional and angiogenic profile, checked by combined microarray and angiogenesis PCR analyses, upregulating VEGFA, FGF2, MMP2, WNT5a and PDGFA and downregulating thrombospoindin-2. The pro- and anti-angiogenic HOXB7-related gene signature was also validated in a large independent dataset of MM patients. Accordingly, MM-induced vessel formation was significantly increased by HOXB7 overexpression both in vitro angiogenic and chorioallantoic membrane assays, as well as the HOXB7 silencing by small interfering RNA inhibited the production of angiogenic factors, and the pro-angiogenic properties of MM cells. Finally, in SCID-NOD mice we confirmed that HOXB7 overexpression by MM cells stimulated tumor growth, increased MM-associated angiogenesis and the expression of pro-angiogenic genes by microarray analysis supporting the critical role of HOXB7 in the angiogenic switch in M

Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?

Background: Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Materials and methods: Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Results: Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng m

Clinical and Economic Impact of Early Diagnosis of Chronic Kidney Disease in General Practice: The Endorse Study

Francesco Pesce,1 Giacomo Matteo Bruno,2 Giorgio Lorenzo Colombo,2 Sergio Di Matteo,3 Anna Rita Maurizi,4 Valentina Mongelli,4 Silvia Mele,5 Lavinia Narici,5 Stefano Bianchi,6 Mario Bonomini,7 Giuseppe Castellano,8 Luca De Nicola,9 Giovanni Gambaro,10 Giuseppe Grandaliano,11 Gaetano La Manna,12 Antonello Pani,13 Andrea Ranghino,14 Loreto Gesualdo15 1Division of Renal Medicine, “Fatebenefratelli Isola Tiberina—Gemelli Isola”, Rome, 00186, Italy; 2Department of Drug Sciences, University of Pavia, Pavia, Italy; 3S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 4Cardiovascular, Renal and Metabolism Medical Affairs, AstraZeneca, Milan, Italy; 5Value & Access, AstraZeneca, Milan, Italy; 6Nephrology and Dialysis Unit, Department of Internal Medicine, ASL Toscana Nordovest, Regione Toscana, Livorno, Italy; 7Department of Medicine, Section of Nephrology and Dialysis, G. D’Annunzio University, Chieti, 66013, Italy; 8UOC of Nephrology, Dialysis, and Kidney Transplant, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 9Department of Advanced Medical and Surgical Sciences, Nephrology and Dialysis Unit, University Vanvitelli, Naples, Italy; 10Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy; 11Department of Translational Medicine and Surgery, Università Cattolica Sacro Cuore, Rome, Italy; 12Nephrology Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 13Department of Nephrology and Dialysis, G. Brotzu Hospital, Cagliari, Italy; 14Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti Ancona, Ancona, Italy; 15Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (Dimepre-J), University of Bari “aldo Moro”, Bari, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email [email protected]: The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis.Methods: Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases.Results: The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention’s impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure.Discussion: A budget impact analysis projected cumulative five-year savings of € 1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at € 106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression.Conclusion: The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale. Keywords: eGFR, uACR, awareness, chronic kidney disease, general practice, economic impact, training intervention, early diagnosi

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

Background: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. Results: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). Conclusions: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract: [Figure not available: see fulltext.]