Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Características clínicas y epidemiológicas asociadas con internación en niños con COVID-19 en un hospital pediátrico de alta complejidad: Estudio de cohorte enero-marzo 2022 / Clinical and epidemiologic characteristics associated with hospital admission in children with COVID19 in a tertiary-care pediatric hospital: A January-March 2022 cohort study

Introducción: La proporción de casos reportados de niños y adolescentes con COVID-19 aumenta progresivamente. La hospitalización relacionada con COVID-19 en niños es infrecuente, pero causa morbilidad y sobrecarga al sistema de salud. Objetivos: Describir las características clínicas y evolutivas de los niños con diagnóstico de COVID-19 en un hospital pediátrico de alta complejidad. Comparar los pacientes que requirieron internación y los que no. Material y métodos: Cohorte prospectiva. Se incluyeron todos los pacientes con diagnóstico virológico de COVID-19 desde 1.1.2022 a 1.3.22 en un hospital pediátrico de alta complejidad. Se compararon los antecedentes, características clínicas y evolutivas de los pacientes según requirieran o no internación. Se utilizó STATA 16. Resultados: n: 1764 pacientes, de ellos 958 eran varones (54%). La mediana de edad fue 56 meses (RIC 17-116). Tenían enfermedad de base 789 pacientes (46%). Las más frecuentes fueron: enfermedad oncohematológica 215 (12%), neurológica 103 pacientes (6%) , enfermedad pulmonar crónica 68 (4%), cardiopatías congénitas 65 (4%) y síndrome genético 57 pacientes (3%). Eran inmunosuprimidos: 292 (17%). Presentaron síntomas relacionados con COVID-19 1319 pacientes (79%). Requirieron internación 591 (34%). Tuvieron coinfección con otros virus respiratorios 33 pacientes (2%). Ingresaron a Cuidados intensivos en relación a la COVID-19 22 pacientes (1.3%) y fallecieron en relación con la infección 8 (0.5%). En el análisis univariado, la presencia de comorbilidades, la coinfección viral y la inmunosupresión se asociaron estadísticamente con el requerimiento de internación. El antecedente de 2 o más dosis de vacuna para SARS-CoV-2 fue un factor protector para la internación en los mayores de 3 años. En el modelo multivariado, los pacientes menores de 3 años (OR 6.5, IC95% 1.2-36.8, p 0.03), con comorbilidades (OR 2.04, IC 95% 1.7- 3.3, p 0.00) y los huéspedes inmunocomprometidos (OR 2.89, IC95% 2.1-4.1, p 0.00) tuvieron más riesgo de internación. Ajustado por el resto de las variables, haber recibido dos o más dosis de vacuna fue un factor protector para la internación (OR 0.65, IC 95% 0.49-0.87, p<0.01). Conclusiones: En este estudio de cohorte prospectivo de niños con diagnóstico confirmado de COVID-19 predominó la enfermedad sintomática. Fueron admitidos en relación con el COVID-19, 34% de los pacientes. La vacunación con dos o más dosis fue un factor protector para la internación en el modelo multivariado. Además, se asociaron estadísticamente con la hospitalización, la edad menor de 3 años, las comorbilidades previas y la inmunosupresión (AU)

Introduction: The rate of reported cases of children and adolescents with COVID-19 is progressively increasing. COVID-19-related hospital admission in children is uncommon, but leads to morbidity and places a burden on the healthcare system. Objectives: To describe the clinical characteristics and outcome of children diagnosed with COVID-19 in a pediatric tertiary-care hospital and to compare patients who required hospital admission with those who did not. Material and methods: A prospective cohort study. All patients with a virological diagnosis of COVID-19 seen between 1.1.2022 and 1.3.22 in a tertiary-care pediatric hospital were included. We compared patient history, clinical characteristics, and outcome according to whether or not they required hospital admission. STATA 16 was used. Results: n: 1764 patients, 958 of whom were male (54%). The median age was 56 months (IQR, 17- 116). Overall, 789 patients had an underlying disease (46%), the most frequent of which were hematology-oncology disease in 215 patients (12%), neurological disease in 103 (6%), chronic lung disease in 68 (4%), congenital heart disease in 65 (4%), and a genetic syndrome in 57 (3%); 292 were immunosuppressed (17%). Overall, 1319 patients (79%) had COVID-19-related symptoms and 591 (34%) required hospital admission. A coinfection with other respiratory viruses was observed in 33 patients (2%). Intensive care admission due to COVID-19 was required in 22 patients (1.3%) and 8 (0.5%) died with COVID-19. In univariate analysis, the presence of comorbidities, viral coinfecton, and immunosuppression were statistically significantly associated with the need for hospitalization. A history of two or more doses of the SARSCoV2 vaccine was a protective factor against hospital admission in children older than 3 years. In the multivariate model, patients younger than 3 years (OR 6.5, 95% CI 1.2-36.8, p 0.03), with comorbidities (OR 2.04, 95%CI 1.7-3.3, p 0.00) and immunocompromised hosts (OR 2.89, 95% CI 2.1-4.1, p 0.00) had a higher risk of hospital admission. When adjusting for the remaining variables, having received two or more doses of the vaccine was found to be a protective factor against hospital admission (OR 0.65, 95% CI 0.49-0.87, p<0.01). Conclusions: In this prospective cohort study of children with a confirmed diagnosis of COVID-19, symptomatic disease predominated. Thirty-four percent of the patients were admitted for COVID-19. Vaccination with two or more doses was a protective factor against hospitalization in the multivariate model. In addition, age younger than 3 years, previous comorbidities, and immunosuppression were statistically associated with hospital admission (AU)

Factores de riesgo de bacteriemia en niños con cáncer y neutropenia febril / Risk factors for bacteremia in children with cancer and febrile neutropenia

La bacteriemia representa una importante causa de morbimortalidad en pacientes oncológicos. Durante el episodio de neutropenia inducida por quimioterapia, un 15%­25% de los pacientes tendrá bacteriemia. Objetivo: identificar factores de riesgo asociados con bacteriemia en pacientes oncológicos pediátricos con neutropenia y fiebre. Material y métodos: estudio de cohorte prospectivo. Se incluyeron pacientes con enfermedades hematooncológicas y neutropenia febril, internados en un hospital pediátrico de alta complejidad entre julio de 2018 y mayo de 2019. Se excluyeron receptores de trasplante de médula ósea. Se compararon las características clínicas según se documentara bacteriemia (B) o no. Resultados: Se incluyeron 160 pacientes (p). Eran varones 93 (58%). La mediana de edad fue 81,5 meses (RIC 36-127,5). La enfermedad de base (EB) más frecuente fue: leucemia linfoblástica aguda (LLA) 88 (55%). Se identificaron 20 (12,5%) pacientes con bacteriemia (B). En el análisis univariado hubo asociación entre B y LMA (p=0,003) y la internación en UCI (p=0,0001). En el modelo multivariado, ajustado por el resto de las variables, se identificaron la LMA (OR 8,24, IC95% 2,5-26,4; p<0,001) y la tiflitis (OR 5,86, IC95% 1,2-27,3; p=0,02) como factores relacionados con bacteriemia. Los principales microorganismos identificados fueron: estreptococos del grupo viridans 6 (30%), Escherichia coli 4 (20%) y estafilococos coagulasa negativos 3 (15%). Quince (75%) fueron bacteriemias secundarias a un foco clínico. El foco más frecuente fue el mucocutáneo (n=7, 35%). En esta cohorte de niños con cáncer y neutropenia febril, los factores asociados con bacteriemia fueron: la LMA, la tiflitis y la internación en UCI (AU)

Bacteremia is an important cause of morbidity and mortality in oncology patients. During an episode of chemotherapy-induced neutropenia, 15%-25% of patients will develop bacteremia. Objective: to identify risk factors associated with bacteremia in pediatric oncology patients with neutropenia and fever. Material and methods: prospective cohort study. Patients with hematology-oncology diseases and febrile neutropenia, admitted to a tertiary-care pediatric hospital between July 2018 and May 2019 were included. Bone marrow transplant recipients were excluded. Clinical characteristics were compared according to whether or not bacteremia was recorded. Results: 160 patients were included of whom 93 (58%) were male. Median age was 81.5 months (IQR 36-127.5). The most common underlying disease was acute lymphoblastic leukemia (ALL) in 88 patients (55%). Twenty (12.5%) patients with bacteremia were identified. In univariate analysis, an association was found between bacteremia and acute myeloid leukemia (AML) (p=0.003) and ICU admission (p=0.0001). In the multivariate model, adjusted for the remaining variables, AML (OR 8.24; 95%CI 2.5-26.4; p<0.001) and typhlitis (OR 5.86; 95%CI 1.2-27.3; p=0.02) were identified as factors related to bacteremia. The main microorganisms identified were viridans group streptococci in 6 (30%), Escherichia coli in 4 (20%), and coagulase negative staphylococci in 3 (15%). In 15 cases (75%), bacteremia was secondary to a clinical focus. The most frequent focus was mucocutaneous (n=7, 35%). In this cohort of children with cancer and febrile neutropenia, the factors associated with bacteremia were AML, typhlitis, and ICU admission (AU)

Outcome and technical consideration of conversion total hip arthroplasty after failed fixation of intracapsular and extracapsular hip fractures: Are they really that different?

INTRODUCTION: Conversion Total Hip Arthroplasty (cTHA) is a rescue strategy for proximal femur osteosynthesis failures. However, it is unclear whether cTHAs performed for extra-capsular fracture fixation failures (ECF) or for intra-capsular fracture fixation failures (ICF) share the same complexity and efficacy. The purpose of our study was to compare cTHAs performed on pre-existing ICFs and pre-existing ECFs, focusing on surgical complications and functional outcomes in both groups. METHODS: An observational retrospective study was conducted on cTHA patients, treated between 2014 and 2018, divided into 2 groups: ICF-group and ECF-group. The main outcomes were: type of implant used, duration of surgery, need for transfusions, incidence of complications, functional outcomes. RESULTS: 28 patients were included (15 in the ECF group and 13 in the ICF group); the average follow-up was of 31 ± 17.3 months. No significant differences were identified in terms of the type of implant used and duration of surgery. The number of transfused patients was 4 in the ICF group and 12 in the ECF group (p = 0.02); the average transfused units were 0.4 ± 0.7 in the ICF group and 1.3 ± 0.9 in the ECF group (p = 0.01). The incidence of complications - an infection and a dislocation, both of which occurred in the ICF group - and functional outcomes did not present significant differences. CONCLUSION: The conversion surgery on ECFs patients is technically more difficult for the surgeon and prone to greater blood loss. The outcomes are satisfactory and overlap between the two groups.

Risk of multiple sclerosis relapses when switching from fingolimod to cell-depleting agents: the role of washout duration.

BACKGROUND: Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred. OBJECTIVE: To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register. METHODS: The risk of relapses was assessed in relation to different washout durations (< 6, 6-11, 12-17 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation. RESULTS: We included 329 patients in the analysis (226F, 103 M; mean age 41 ± 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12-17 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration. CONCLUSION: The risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents.

Efficacy of mechanical thrombectomy in patients with ischemic stroke and cancer.

Cancer-related coagulopathy is a known cause of stroke and can lead to formation of thrombi with a unique composition. The effectiveness of mechanical thrombectomy in cancer patients is still unknown. The aim of the study was to evaluate the rate of successful reperfusion and the clinical outcome in cancer patients with stroke treated with endovascular therapies, compared to patients without cancer. We performed a retrospective analysis of consecutive patients with ischemic stroke treated with endovascular therapies at our hospital between January 2008 and January 2016. A sub-group analysis was performed including only patients with cryptogenic stroke. We included in the final analysis 14 patients with active cancer and 267 patients without cancer. Successful reperfusion was achieved in 79% of patients without cancer, and 71% of patients with active cancer (P = 0.68). Patients with cryptogenic stroke and active cancer had a lower reperfusion rate compared to patients with cryptogenic stroke without active cancer, although not significantly so (2/4 cancer patients, 50% vs 37/50, 74%, p: 0.31). Mortality rate was higher among cancer patients. Hemorrhagic transformation occurred in similar proportions in the two groups. Endovascular treatment in cancer patients seems, thus, effective.

Características clínicas y evolutivas de niños con infección por SARS-CoV-2 en un hospital de alta complejidad: estudio de cohorte / Clinical and outcome characteristics of children with SARS CoV-2 infection in a tertiary-care hospital: a cohort study

Introducción: Las infecciones por SARS-CoV-2 representan un problema de salud pública a nivel mundial. En los niños se reporta menor incidencia y cuadros clínicos más leves. Se realizó el presente estudio con el objetivo de describir las características clínicas y evolutivas de los niños con diagnóstico de infección por SARS CoV-2 en el Hospital Juan P. Garrahan. Material y métodos: estudio de cohorte prospectivo. Se incluyeron todos los pacientes con diagnóstico confirmado por PCR de COVID-19 desde 20.4.20 hasta el 3.07.21 y con seguimiento en el hospital de Pediatría Juan P. Garrahan. Resultados: n: 1644. Eran varones 836 (51%). La mediana de edad fue 75 meses (RIC 22- 143). Tenían alguna enfermedad de base previa al diagnóstico de COVID-19: 884 pacientes (53,7%), la más frecuente fue la enfermedad oncohematológica. Estaban asintomáticos 423 pacientes (25,7%). De los pacientes sintomáticos, 1071 (65,1%) presentaron cuadro leve, 5 (0,3%) moderado, 69 (4,2%) grave y 76 (4,6%) crítico. La fiebre fue el hallazgo más frecuente n: 782; (47,5%). Se internaron 900 pacientes (54,7%), 33 en UCI (2%). Fallecieron 7 pacientes (0,4%), todos ellos con comorbilidades graves. Conclusiones: En este estudio de cohorte de niños con infección por SARS-CoV-2 confirmada, predominaron los pacientes con enfermedad de base y las formas leves de COVID-19. El ingreso a UCI fue menor al 2%. Fallecieron 7 pacientes (0.4%) todos ellos con comorbilidades y coinfecciones (AU)

Introduction: SARS-CoV-2 infections represent a worldwide public health problem. A lower incidence and milder clinical pictures are reported in children. The aim of this study was to describe clinical and outcome characteristics of children diagnosed with SARS-CoV-2 infection at Hospital de Pediatría Juan P. Garrahan. Methods: A prospective cohort study was conducted. All patients with a PCR-confirmed diagnosis of COVID-19 seen between 20.4.20 and 3.07.21 and followed-up at Hospital de Pediatría Juan P. Garrahan were included. Results: n: 1644; 836 males (51%) were male. Median age was 75 months (IQR, 22-143). Overall, 884 patients (53.7%) had an underlying disease prior to COVID-19 diagnosis, most frequently hematologic/ oncologic disease. 423 patients (25.7%) were asymptomatic. Of the symptomatic patients, 1071 (65.1%) had mild, 5 (0.3%) moderate, 69 (4.2%) severe, and 76 (4.6%) critical disease. Fever was the most frequent finding (n: 782; 47.5%). A total of 900 patients (54.7%) were admitted, 33 of whom to the ICU (2%). Seven patients (0.4%) died, all with severe comorbidities. Conclusions: In this cohort study of children with confirmed SARSCoV-2 infection, patients with underlying disease and mild forms of COVID-19 predominated. ICU admission occurred in less than 2%. Seven patients (0.4%) died, all of them with comorbidities and coinfections. (AU)

Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy.

BACKGROUND: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. AIM: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital. METHODS: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods. FINDINGS: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. CONCLUSION: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment.

A multicenter survey on access to care in Multiple Sclerosis-related trigeminal neuralgia.

The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology. Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres. Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them. This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization.

Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing-remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF-treated patients. METHODS: Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6 months. Multivariate Cox models were performed to evaluate the impact of 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. RESULTS: In all, 476 patients (312 females, age at DMF start 38.4 ± 9.97 years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (hazard ratio 0.87, P = 0.01). A worse outcome in patients with lower ALC drop (<11.5%), compared with higher tertiles (11.5%-40.5% and >40.5%), was observed (P = 0.008). The nadir of ALC drop (-33.6%) and 35% of grade III lymphopaenia cases occurred after 12 months of treatment. CONCLUSION: A higher lymphocyte count drop at 6 months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.

Relaxation and revival of quasiparticles injected in an interacting quantum Hall liquid.

The one-dimensional, chiral edge channels of the quantum Hall effect are a promising platform in which to implement electron quantum optics experiments; however, Coulomb interactions between edge channels are a major source of decoherence and energy relaxation. It is therefore of large interest to understand the range and limitations of the simple quantum electron optics picture. Here we confirm experimentally for the first time the predicted relaxation and revival of electrons injected at finite energy into an edge channel. The observed decay of the injected electrons is reproduced theoretically within a Tomonaga-Luttinger liquid framework, including an important dissipation towards external degrees of freedom. This gives us a quantitative empirical understanding of the strength of the interaction and the dissipation.

Informing MS patients on treatment options: a consensus on the process of consent taking.

In the last years, change in multiple sclerosis (MS) therapeutic scenario has highlighted the need for an improved doctor-patient communication in advance of treatment initiation in order to allow patient's empowerment in the decision-making process. AIMS: The aims of our project were to review the strategies used by Italian MS specialists to inform patients about treatment options and to design a multicentre shared document that homogenizes the information about disease-modifying treatment (DMTs) and the procedure of taking informed consent in clinical practice. RESULTS: The new resource, obtained by consensus among 31 neurologists from 27 MS Centres in Italy with the supervision of a medico-legal advisor, received the aegis of Italian Neurological Society (SIN) and constitutes a step toward a standardized decision process around DMTs in MS.

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.

BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.

ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band-negative patients with suspected multiple sclerosis.

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB-negative patients with suspected MS. METHODS: The CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB-negative patients with suspected/possible MS and in 54 OCB-positive patients with MS. RESULTS: The CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut-off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB-negative MS (23/92) and in 98% of OCB-positive patients with MS. Using a qualitative approach and a kappa index cut-off of 5.9, based on literature data, we likewise found that 24% of OCB-negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB-negative patients without MS (P < 0.001). No reliable data could be obtained for the lambda index; lambda FLCs were below the detection limit (0.68 mg/L) in 90% of CSF samples. CONCLUSIONS: The kappa index could contribute to the identification of OCB-negative patients with a high probability of an MS diagnosis. Using more sensitive techniques might even improve the diagnostic performance of the kappa index and better define the role of the lambda index.

Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study.

BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

Controlling the distance of highly confined droplets in a capillary by interfacial tension for merging on-demand.

Droplet microfluidics is a powerful technology that finds many applications in chemistry and biomedicine. Among different configurations, droplets confined in a capillary (or plugs) present a number of advantages: they allow positional identification and simplify the integration of complex multi-steps protocols. However, these protocols rely on the control of droplet speed, which is affected by a complex and still debated interplay of various physico-chemical parameters like droplet length, viscosity ratio between droplets and carrier fluid, flow rate and interfacial tension. We present here a systematic investigation of the droplet speed as a function of their length and interfacial tension, and propose a novel, simple and robust methodology to control the relative distance between consecutive droplets flowing in microfluidic channels through the addition of surfactants either into the dispersed and/or into the continuous phases. As a proof of concept application, we present the possibility to accurately trigger in space and time the merging of two confined droplets flowing in a uniform cross-section circular capillary. This approach is further validated by monitoring a conventional enzymatic reaction used to quantify the concentration of H2O2 in a biological sample, showing its potentialities in both continuous and stopped assay methods.

Active immunization status against measles, mumps, rubella, hepatitis B in internationally adopted children, surveyed at the university hospital of Palermo, Sicily.

INTRODUCTION: The internationally adopted child is a fragile subject who often shows an incomplete health documentation, which hinders the complete assessment of health status. MATERIALS AND METHODS: Between January 2010 and June 2016, at the University Hospital "AOUP P. Giaccone" of Palermo, we reviewed the health documentations of 111 children recently arrived in Italy following the conclusion of the international adoption procedure. 62.2% of the children were male, of various nationalities and with an average age of 7 years (± 3.4). This study aims to detect, in the observed sample, the reliability of the vaccinal documentation and the real acquired immunization. We intend to estimate the presence of IgG against Measles, Mumps, Rubella and Hepatitis B viruses. RESULTS: Percentages of subjects with a complete correspondence between documentation attesting the successful vaccination and the effective immunization were: 78% for measles, 66% for mumps, 84% for rubella, 71% for hepatitis B. Percentages of subjects without vaccinal documentation but with positive evidence of IgG were: 50% for measles, 38% for mumps, 71% for rubella, 50% for hepatitis B. CONCLUSIONS: The partial correspondence found between vaccinations performed and real immune status can be attributed to several reasons: poor reliability of the received health documentation, the complex economic situation of the health services in the countries of origin, the incorrect vaccines storage or the administration beyond the expiration date, the poor immunological response due to concomitant diseases or severe malnutrition, the probable non-administration of the expected booster dose. Particular attention needs to be paid to this population, which may represent a risk group susceptible to vaccine-preventable diseases.

Dynamics of Ferrofluid Drops on Magnetically Patterned Surfaces.

The motion of liquid drops on solid surfaces is attracting a lot of attention because of its fundamental implications and wide technological applications. In this article, we present a comprehensive experimental study of the interaction between gravity-driven ferrofluid drops on very slippery oil-impregnated surfaces and a patterned magnetic field. The drop speed can be accurately tuned by the magnetic interaction, and more interestingly, drops are found to undergo a stick-slip motion whose contrast and phase can be easily tuned by changing either the strength of the magnetic field or the ferrofluid concentration. This motion is the result of the periodic modulation of the external magnetic field and can be accurately analyzed because the intrinsic pinning due to chemical defects is negligible on oil-impregnated surfaces.