Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort.

BACKGROUND: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. PATIENTS AND METHODS: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. RESULTS: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR ≥3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII ≥884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII + PD-L1 + LDH and SII + PD-L1 combinations. CONCLUSION: The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.

Identification of volatile biomarkers of Giardia duodenalis infection in children with persistent diarrhoea.

Currently, chronic diarrhoea syndrome in children is a very common pathology whose aetiology is sometimes difficult to identify. Methodologies for the diagnosis of infections have diversified, and gas chromatography/mass spectrometry (GC/MS) is a very useful tool. The aim of this study was to identify volatile biomarkers of the presence of Giardia duodenalis in the faeces of patients with chronic diarrhoea (with and without giardiasis) using static headspace extraction followed by GC/MS. The analysis of the volatiles extracted from the headspace had enough sensitivity to detect differences in the volatile profiles in the faeces of the patients with and without Giardia duodenalis infection and discriminate between them. Dimethyl disulphide and trisulphide were found in the faeces of patients without giardiasis but not in the faeces of patients with G. duodenalis. Finally, three possible biomarkers, acetic acid, 1,4-dimethoxy-2,3-butanediol and 1,3-dimethoxy-2-propanol, were proposed to identify patients with giardiasis; these compounds were not present in the patients without the parasite. Multivariate analysis revealed that principal component 1 separated the stool samples according to the presence of infection by G. duodenalis despite the inter-individual variability in biological specimens such as faeces.

Safety of rituximab in the routine treatment of rheumatoid arthritis in Italy in patients refractory to anti-TNFa drugs: results from the observational retrospective-prospective RUBINO study.

The paper reports the results from the observational retrospective-prospective RUBINO study conducted in Italy to assess the safety of rituximab in the treatment of rheumatoid arthritis (RA) in routine clinical practice. The percentage of patients who manifested at least one grade 3 or 4 adverse event (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3) during the observation period (primary objective) was evaluated. The percentage of patients manifesting a severe AE (SAE), clinical response to rituximab treatment, clinical remission according to disease activity score for 28 joints (DAS28) criteria, markers of disease and quality of life were also assessed. Fifty-three Italian rheumatology centers took part in the study. Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis factor b (anti-TNFa) drugs were enrolled. Participating patients had previously received at least one cycle of rituximab, and treatment was still ongoing at the time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE, 14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The overall percentage of patients manifesting AEs (40%) was lower compared to the DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference may be due to the shorter observation period applied in the CERERRA registry (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of RA activity (erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire score, DAS28) improved significantly during the study.

[Epidemiology of children's intestinal parasitism in the Guadalquivir Valley, Spain]. / Epidemiología del parasitismo intestinal infantil en el Valle del Guadalquivir, España.

BACKGROUND: Intestinal parasitism represents a public health problem that should be periodically assessed in each region. In the present paper, a study about prevalence of intestinal parasites, has been carried out in children from the natural region of the Guadalquivir Valley. METHODS: During the period 1994-1996, 1,917 children without symptoms, aging between 6 and 10, were studied by means of coprological analysis and Graham method, all of them living in 20 villages in the Guadalquivir valley. RESULTS: The overall prevalence of intestinal parasitism have been of 27.12%. The reported parasites and their prevalence are as follows: Enterobius vermicularis (20.44%), Giardia lamblia (5.05%), Entamoeba coli (2.45%), Endolimax nana (1.61%), Entamoeba histolytica (0.31%), Entamoeba hartmanni (0.05%), Iodamoeba bütschlii (0.05%). CONCLUSIONS: The overall prevalence of intestinal parasites is similar to that found in other spanish region, if only a little bit more favourable probably due to the long lasting drought and the improvements in health resources, no geohelminths have been detected unlike other protozoan infections, giardiasis maintains a relatively high prevalence.

Algumas consideraçöes a respeito da reaçäo de Rubino / Rubino's reaction

Säo comentados alguns aspectos relativos a reaçäo de Rubino, visando tanto uma melhor identificaçäo dos elementos envolvidos como despertar o interesse dos pesquisadores para esta prova. Os seguintes aspectos säo discutidos: 1) influência da temperatura sobre os elementos da reaçäo; 2) correlaçäo entre a reaçäo de Rubino e: a) alteraçöes humorais observadas nas hanseníase, b) imunidade mediada por células; 3) variaçöes na reatividade sorológica; 4) valor prognóstico e crério de cura

Estudo das reaçöes de Fernandez e Mitsuda em pacientes hansenianos e seus contatos / Fernandez's and Mitsuda's reaction in hanseniasis patients and their contacts

Pacientes hansenianos e contatos de pacientes virchowianos, totalizando 467 pessoas foram submetidos a reaçäo de Mitsuda. Esses indivíduos foram divididos foram divididos em 5 grupos: grupo 1: - 59 pessoas, familiares de pacientes virchowianos; grupo 2: - 171 pessoas, funcioncários que trabalham há mais de um ano no Hospital Lauro de Souza Lima; grupo 3: - 127 pacientes hansenianos em atividade, Mitsuda negativos; grupo 4: - 63 pacientes hansenianos em atividade, Mitsuda positivos; grupo 5: - 47 pacientes virchowianos inativos, Mitsuda negativos. Pela análise obtida dos dados pode-se evidenciar que: a) pacientes hansenianos, tanto os Mitsuda positivos como os negativos, näo apresentam positividade a reaçäo de Fernandez; b) a reaçäo precoce pode ser observada com maior freqüência em indivíduos do grupo 1 que naqueles do grupo 2. O antígeno de Mitsuda provoca a viragem da reaçäo de Fernandez em cerca de 30% dos contatos indiretos; c) o percentual de reaçöes de Mitsuda negativas (sem induraçäo) näo difere entre os grupos 1 e 2 embora induraçöes menores de 5 mm tenham sido 10 vezes mais freqüentes em indivíduos do grupo 1. Uma segunda aplicaçäo do antígeno em pessoas Mitsuda negativas mostrou a viragem dos testes em 100% dos indivíduos testados

[Fernandez and Mitsuda reactions in patients with leprosy and their contacts]. / Estudo das reaçóes de Fernandez e Mitsuda em pacientes hansenianos e seus contatos.

Hanseniasis patients and contacts of Virchowian patients, totaling 467 persons have been submitted to Mitsuda's reaction. These individuals have been divided into five groups: group 1 compounded of 59 persons, relatives of Virchowian patients; group 2 - 171 persons, employees of the Hospital Lauro de Souza Lima working there for more than one year; group 3 - 127 hanseniasis patients in activity, Mitsuda negative; group 4 - 63 hanseniasis patients in activity, Mitsuda positive; group 5 - 47 Virchowian patients, inactive, Mitsuda negative. The analysis of the data showed that: a) hanseniasis patients, both Mitsuda positive and negative, do not present positivity to Fernandez's reaction; b) early reaction can be observed more frequently in individuals of group 1 than in those of group 2. Mitsuda's antigen causes the reversal of Fernandez's reaction in about 30% of indirect contacts; c) the percentage of negative Mitsuda's reactions (without induration) does not differ between groups 1 and 2, though indurations smaller than 5 mm have been as many as 10 times more frequent in individuals of group 1. A second application of the antigen in Mitsuda negative persons showed the reversal of the test in 100% of the tested subjects.

[Rubino's reaction]. / Algumas considerações a respeito da reação de Rubino.

Some aspects related to the Rubino's reaction are commented, viewing both a better identification of the involved elements and the arousing of the investigators interest for this test. The following aspects are discussed: 1) the influence of temperature upon the elements of the reaction; 2) Correlation between Rubino's reaction and: a) humoral alterations observed in leprosy; b) cell mediated immunity; 3) variations of the serologic reactivity; 4) prognosis value and healing criterion.

[The Rubino reaction. Criterion for inactivation in lepromatous patients]. / Reação de Rubino. Critério de branqueamento para pacientes virchowianos.

Approximately 55% of active lepromatous patients respond positively to the Rubino reaction. With arrested cases this rate of positivity lowers considerably to about 15%. In an effort to associate this reaction with the presence of bacilli, a study of 796 cases was undertaken. The patients were divided into: a control group, active tuberculoid cases, arrested tuberculoid cases, active borderline cases, arrested borderline cases, active lepromatous cases, and arrested lepromatous cases. The patients were submitted to the following tests: Rubino reaction, presence of cryoglobulins, and VDRL and PCR positivity. By the results obtained we may conclude that: a) A positive Rubino reaction may be present in all the forms of leprosy studied, this reaction having an inverse relationship with the organism's resistance to "M. leprae". b) The Rubino reaction has specificity to leprosy. c) This reaction does not depend on the number of bacilli present in the host. d) A positive Rubino reaction is not related to the presence of cryoglobulins in the serum, nor to VDRL or PCR positivity, nor to the length of time the patient's disease has been arrested. The authors present these findings and suggest that this reaction be used as one of the criteria for determining cure.