Pseudoprogression and hyperprogression secondary to immunotherapy in lung cancer

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) has undergone changes that have improved the prognosis of patients. With the advent of immunotherapy, it has been possible to prolong significantly the overall and progression-free survival as well as quality of life. Nevertheless, its use represents clinical challenges which may turn into adverse events, such as progression and pseudo-progression, which are uncontrolled and often deleterious immune responses that simulate tumoral progression, generate worsening of symptoms and performance status of patients and even may lead to non-cancer related death of patients. MATERIALS AND METHODS: We assessed 128 records (clinical trials, reports, meta-analyses) in order to provide an updated review of the treatment of NSCLC, current definitions proposed for pseudo and hyperprogression (which are not homogeneous so far), incidence, theories about their physiopathogenesis, importance of making a judicious diagnostic workup, imaging criteria as well as biochemical markers in order to predict their appearance, concluding with a brief discussion about the topic addressed. CONCLUSIONS: Since there is no definition or standardized diagnostic and imaging criteria, these entities are a topic of major interest in the area of oncologic immunotherapy, for which the following review has been generated

Stroke prevalence among the Spanish elderly: an analysis based on screening surveys

BACKGROUND: This study sought to describe stroke prevalence in Spanish elderly populations and compare it against that of other European countries. METHODS: We identified screening surveys -both published and unpublished- in Spanish populations, which fulfilled specific quality requirements and targeted prevalence of stroke in populations aged 70 years and over. Surveys covering seven geographically different populations with prevalence years in the period 1991–2002 were selected, and the respective authors were then asked to provide descriptions of the methodology and raw age-specific data by completing a questionnaire. In addition, five reported screening surveys in European populations furnished useful data for comparison purposes. Prevalence data were combined, using direct adjustment and logistic regression. RESULTS: The overall study population, resident in central and north-eastern Spain, totalled 10,647 persons and yielded 715 cases. Age-adjusted prevalences, using the European standard population, were 7.3% for men, 5.6% for women, and 6.4% for both sexes. Prevalence was significantly lower in women, OR 0.79 95% CI 0.68–0.93, increased with age, particularly among women, and displayed a threefold spatial variation with statistically significant differences. Prevalences were highest, 8.7%, in suburban, and lowest, 3.8%, in rural populations. Compared to pooled Spanish populations, statistically significant differences were seen in eight Italian populations, OR 1.39 95%CI (1.18–1.64), and in Kungsholmen, Sweden, OR 0.40 95%CI (0.27–0.58). CONCLUSION: Prevalence in central and north-eastern Spain is higher in males and in suburban areas, and displays a threefold geographic variation, with women constituting the majority of elderly stroke sufferers. Compared to reported European data, stroke prevalence in Spain can be said to be medium and presents similar age- and sex-specific traits

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

One major goal of research on Chagas disease is the development of effective chemotherapy to eliminate the infection from individuals who have not yet developed cardiac and/or digestive disease manifestations. Cure evaluation is the more complex aspect of its treatment, often leading to diverse and controversial results. The absence of reliable methods or a diagnostic gold standard to assess etiologic treatment efficacy still constitutes a major challenge. In an effort to develop more sensitive tools, polymerase chain reaction (PCR)-based assays were introduced to detect low amounts of Trypanosoma cruzi DNA in blood samples from chagasic patients, thus improving the diagnosis and follow-up evaluation after chemotherapy. In this article, I review the main problems concerning drug efficacy and criteria used for cure estimation in treated chagasic patients, and the work conducted by different groups on developing PCR methodologies to monitor treatment outcome of congenital infections as well as recent and late chronic T. cruzi infections

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Características clínico-patológicas de 127 casos de neoplasias neuroendocrinas del aparato gastrointestinal y páncreas (NNE-GEP) estudiadas en un hospital de oncología

Introducción: Las neoplasias neuroendocrinas (NNE) se presentan en todo lo largo del aparato gastrointestinal (GI), desde el esófago hasta el ano y también en el páncreas. Objetivos: Clasificar a las NNE de acuerdo con los criterios de la Organización Mundial de la Salud (OMS) 2010, y evaluar su distribución anatómica y características clínico-patológicas. Material y métodos: Se buscaron en los archivos de Patología todos los casos con diagnóstico de tumor carcinoide y carcinoma neuroendocrino del aparato GI y páncreas, estudiados en un lapso de 11 años (1999-2010). Los casos fueron reclasificados de acuerdo con los criterios de la OMS 2010. Se revisaron los expedientes clínicos de cada paciente. Resultados: Ciento veintisiete casos (68 hombres y 59 mujeres) conformaron el grupo de estudio. El rango de edad varió de 24 a 85, con una mediana de 52 años. Ciento trece (89,00%) ocurrieron en el tracto GI y 14 (11,00%) en el páncreas. El tamaño de los tumores varió de 0,4 cm a 9 cm (mediana: 2,5 cm). El grado histológico de las neoplasias del aparato GI fue: 54,00% grado 1, 31,00% grado 2 y 15,00% grado 3. El grado histológico de los tumores pancreáticos fue: 43,00% grado 1, 36,00% grado 2 y 21,00% grado 3. La sobreexpresión del Ki-67 se correlacionó con el grado tumoral (22,00% grado 3 vs 2,50% grado 1). Conclusiones: El grado histológico en las neoplasias neuroendocrinas del aparato gastrointestinal y páncreas (NNE-GEP) es uno de los factores pronósticos más importantes. El término carcinoide debe ser abolido, ya que no refleja la conducta biológica de las neoplasias en cuestión