Evaluation of interleukin-18 levels in patients affected by multiple myeloma and monoclonal gammopathy of undetermined significance: analysis and review of the literature.

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer. PATIENTS AND METHODS: In this study, interleukin-18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls. RESULTS: Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001). CONCLUSIONS: In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases.

Usefulness of intraoperative voiding cystourethrogram as an indicator of success in the endoscopic treatment of vesicoureteral reflux. / Utilidad de la cistouretrografía miccional intraoperatoria como indicador de éxito del tratamiento endoscópico del reflujo vesicoureteral.

OBJECTIVE: Up until now, serial voiding cystourethrogram (SVCU) has been regarded as the gold standard technique in the diagnosis of vesicoureteral reflux (VUR). The aim of intraoperative SVCU during endoscopic treatment is to detect those patients eligible to receive more biosynthetic material as a result of persistent VUR. The objective of this study was to assess the usefulness of SVCU as a predictor of treatment success. MATERIALS AND METHODS: An analytical, retrospective study of patient medical records was carried out. Patients included had undergone endoscopic VUR surgery from 2000 to 2019, and they were measured in ureteral units. VUR persistence at intraoperative SVCU following treatment was compared with SVCU results after 3 months. RESULTS: Of a total of 167 ureteral units undergoing surgery, persistent reflux immediately after surgery was observed in 17 cases (10% of the sample). Only 3 cases had other urological malformations. In the SVCU carried out after 3 months, reflux was found in 38% of the sample (64 cases). When comparing the results, intraoperative SVCU demonstrated a specificity of 92.6%, and a sensitivity of 15.6%. CONCLUSIONS: Given the low sensitivity (15.6%) of intraoperative SVCU to detect cases of persistent reflux in the mid-term, and considering the risks associated with radiation in the pediatric population - which is extremely sensitive to it -, intraoperative SVCU should be ruled out as a useful indicator of endoscopic treatment success.

OBJETIVO: La cistouretrografía miccional seriada (CUMS) ha sido hasta ahora el gold standard en el diagnóstico del reflujo vesicoureteral (RVU). La finalidad de la CUMS intraoperatoria durante el tratamiento endoscópico es detectar aquellos pacientes subsidiarios de inyectar más material biosintético por persistencia del RVU. En este estudio hemos querido evaluar la utilidad de esta prueba como predictor de éxito del tratamiento. MATERIAL Y METODOS: Estudio analítico retrospectivo mediante la revisión de historias clínicas de pacientes, medidos en unidades ureterales, intervenidos de RVU de forma endoscópica entre los años 2000 y 2019. Se comparó la persistencia de RVU en la CUMS intraoperatoria tras el tratamiento con el resultado de la CUMS a los 3 meses. RESULTADOS: De un total de 167 unidades ureterales intervenidas, se observó persistencia del reflujo inmediatamente tras la intervención en 17 casos (10% de la muestra). Solo 3 asociaban otras malformaciones urológicas. En la CUMS a los 3 meses se observó reflujo en el 38% de la muestra (64 casos). Al comparar los resultados, obtenemos para la CUMS intraoperatoria una especificidad del 92,6% y una sensibilidad del 15,6%. CONCLUSIONES: Dada la baja sensibilidad (15,6%) de la CUMS intraoperatoria para detectar los casos en los que persiste el reflujo a medio plazo y, teniendo en cuenta los riesgos asociados a la radiación que supone en una población especialmente sensible como es la pediátrica, se desestima su utilidad como indicador de éxito del tratamiento endoscópico.

Utilidad de la cistouretrografía miccional intraoperatoria como indicador de éxito del tratamiento endoscópico del reflujo vesicoureteral / Usefulness of intraoperative voiding cystourethrogram as an indicator of success in the endoscopic treatment of vesicoureteral reflux

Objetivo: La cistouretrografía miccional seriada (CUMS) ha sido hasta ahora el gold standard en el diagnóstico del reflujo vesicoureteral (RVU). La finalidad de la CUMS intraoperatoria durante el tratamientoendoscópico es detectar aquellos pacientes subsidiarios de inyectar más material biosintético por persistencia del RVU. En este estudio hemos querido evaluar la utilidad de esta prueba como predictor de éxito deltratamiento. Material y métodos: Estudio analítico retrospectivo mediante la revisión de historias clínicas de pacientes, medidos en unidades ureterales, intervenidos de RVU de forma endoscópica entre los años 2000 y2019. Se comparó la persistencia de RVU en la CUMS intraoperatoria tras el tratamiento con el resultado de la CUMS a los 3 meses. Resultados: De un total de 167 unidades ureterales intervenidas, se observó persistencia del reflujo inmediatamente tras la intervención en 17 casos (10% de la muestra). Solo 3 asociaban otras malformacionesurológicas. En la CUMS a los 3 meses se observó reflujo en el 38% de la muestra (64 casos). Al comparar los resultados, obtenemos para la CUMS intraoperatoria una especificidad del 92,6% y una sensibilidad del 15,6%. Conclusiones: Dada la baja sensibilidad (15,6%) de la CUMS intraoperatoria para detectar los casos en los que persiste el reflujo a medio plazo y, teniendo en cuenta los riesgos asociados a la radiación que supone en una población especialmente sensible como es la pediátrica, se desestima su utilidad como indicador de éxito del tratamientoendoscópico.(AU)

Objective: Up until now, serial voiding cystourethrogram (SVCU) has been regarded as the gold standard technique in the diagnosis ofvesicoureteral reflux (VUR). The aim of intraoperative SVCU during endoscopic treatment is to detect those patients eligible to receive morebiosynthetic material as a result of persistent VUR. The objective of this study was to assess the usefulness of SVCU as a predictor of treatment success. Materials and methods: An analytical, retrospective study of patient medical records was carried out. Patients included had undergoneendoscopic VUR surgery from 2000 to 2019, and they were measured in ureteral units. VUR persistence at intraoperative SVCU followingtreatment was compared with SVCU results after 3 months. Results: Of a total of 167 ureteral units undergoing surgery, persistent reflux immediately after surgery was observed in 17 cases (10%of the sample). Only 3 cases had other urological malformations. In the SVCU carried out after 3 months, reflux was found in 38% of thesample (64 cases). When comparing the results, intraoperative SVCU demonstrated a specificity of 92.6%, and a sensitivity of 15.6%. Conclusions: Given the low sensitivity (15.6%) of intraoperative SVCU to detect cases of persistent reflux in the midterm, and considering the risks associated with radiation in the pediatric population which is extremely sensitive to it, intraoperative SVCU should be ruled outas a useful indicator of endoscopic treatment success.(AU)

How usefulness shapes neural representations during goal-directed behavior.

Value is often associated with reward, emphasizing its hedonic aspects. However, when circumstances change, value must also change (a compass outvalues gold, if you are lost). How are value representations in the brain reshaped under different behavioral goals? To answer this question, we devised a new task that decouples usefulness from its hedonic attributes, allowing us to study flexible goal-dependent mapping. Here, we show that, unlike sensory cortices, regions in the prefrontal cortex (PFC)-usually associated with value computation-remap their representation of perceptually identical items according to how useful the item has been to achieve a specific goal. Furthermore, we identify a coding scheme in the PFC that represents value regardless of the goal, thus supporting generalization across contexts. Our work questions the dominant view that equates value with reward, showing how a change in goals triggers a reorganization of the neural representation of value, enabling flexible behavior.

Melatonin Hormone Acts on Cells of Maternal Blood and Placenta From Diabetic Mothers.

Changes in glucose metabolism of diabetic mothers affect immunological components, proinflammatory factors, and placental hypervascularization that can induce cell death. The hormone melatonin has been identified as a potential modulating agent. The aim of this study was to analyze the oxidative process and the apoptosis in maternal blood and placental cells modulated by melatonin from diabetic mothers. The groups were 40 pregnant women divided into non-diabetic (ND) and type 2 diabetes mellitus (T2DM) groups. Blood and placental cells were obtained by density gradient and maintained in culture treated or not with melatonin (100 ng/mL) for 24 h (37°C, 5% CO2). Oxidative stress was evaluated by superoxide release and CuZn superoxide dismutase (SOD). Apoptosis was assessed by flow cytometry. Maternal hyperglycemia increased superoxide release and apoptosis in MN cells from maternal blood and reduced SOD level and SOD/O2- ratio. Melatonin reduced oxidative stress and apoptosis rates in MN cells in the blood of diabetic mothers. There was a reduction in SOD and SOD/O2- ratio in the placental extravillous layer, and melatonin restored the concentrations of this enzyme. There was greater superoxide release, reduced SOD/O2- ratio, and apoptosis in MN cells placental villous layer. Melatonin increased apoptosis rates in the placental villous layer from hyperglycemic mothers. These data suggest that hyperglycemia altered the processes oxidative in blood and placenta from hyperglycemic mothers. These changes reflected in the mechanisms of induction of apoptosis, especially in the vascularized layers of the placenta, and were modulated by melatonin.

The condom use among young adults and its determinants: an Italian study.

Numerous health risk behaviours have been identified as an issue in early adulthood, especially among university students, a particularly high-risk category for sexual and reproductive health. The aim of this study is to examine the condom use and its determinants among young adult in Italy. The hypothesis is that individuals' demographic characteristics (gender, faculty, to have a committed partner, to be resident) and the risk perception may play a role in condom use. The results indicate that the frequency of condom use is related to the magnitude of risk perception of certain STIs and to demographic characteristics. All the STI risks perception and the risk perception of unintended pregnancy are statistically significant associated with frequency of condom use (p<0.001). By contrast the frequency of condom use is not statistically significant associated with the following demographic characteristics: gender, faculty, to have a committed partner, to be resident. Furthermore association with age groups is observed (p=0.030). Findings suggest that universities have an opportunity to access young people's sexual health risk behaviours and at the same time to impact on sexual health promotion. University health educators and staff at student health centers could play an active role in educational campaigns.

[Conservative management of traumatic priapism in paediatric patients]. / Manejo conservador del priapismo traumático en la edad pediátrica.

INTRODUCTION: High-flow priapism is infrequent in pediatric patients. It is mostly secondary to perineal trauma resulting in laceration of a penile artery and the formation of an arterio-cavernous fistula. It does not constitute a medical emergency in itself, and allows conservative management awaiting spontaneous resolution. CLINICAL CASE: A six-year-old boy with painless persistent erection preceded by perineal trauma. Ultrasound imaging confirmed the clinical suspicion of high flow priapism secondary to arterio-cavernous fistula. After adopting a conservative approach, the patient presented progressive detumescence, as well as ultrasound resolution one month after the episode. COMMENTS: In high-flow priapism, venous drainage of the penis is preserved. The classical approach in adults is based on therapeutic angiography, which presents greater technical complexity and the risk of iatrogenic hypoxia in pediatric patients.

INTRODUCCION: El priapismo de alto flujo es una entidad infrecuente en la edad pediátrica. Es, en su mayoría, secundario a traumatismo perineal que provoca la laceración de una arteria peneana y formación de una fístula arterio-cavernosa. No constituye una emergencia médica, permitiendo un manejo conservador a la espera de su resolución espontánea. CASO CLINICO: Niño de seis años con erección persistente e indolora tras traumatismo perineal. El diagnóstico ecográfico confirma la sospecha de priapismo de alto flujo secundario a fístula arteria-cavernosa. Tras manejo conservador, presenta detumescencia progresiva y resolución ecográfica al mes del episodio. COMENTARIOS: En el priapismo de alto flujo el drenaje venoso del pene se encuentra conservado. El manejo clásico en adultos se fundamenta en la angiografía terapéutica, de mayor complejidad técnica y riesgo de hipoxia iatrogénica en el paciente pediátrico.

Manejo conservador del priapismo traumático en la edad pediátrica / No disponible

Introducción: El priapismo de alto flujo es una entidad infrecuente en la edad pediátrica. Es, en su mayoría, secundario a traumatismo perineal que provoca la laceración de una arteria peneana y formación de una fístula arterio-cavernosa. No constituye una emergencia médica, permitiendo un manejo conservador a la espera de su resolución espontánea. Caso clínico: Niño de seis años con erección persistente e indolora tras traumatismo perineal. El diagnóstico ecográfico confirma la sospecha de priapismo de alto flujo secundario a fístula arteria-cavernosa. Tras manejo conservador, presenta detumescencia progresiva y resolución ecográfica al mes del episodio. Comentarios: En el priapismo de alto flujo el drenaje venoso del pene se encuentra conservado. El manejo clásico en adultos se fundamenta en la angiografía terapéutica, de mayor complejidad técnica y riesgo de hipoxia iatrogénica en el paciente pediátrico

Introduction: High-flow priapism is infrequent in pediatric patients. It is mostly secondary to perineal trauma resulting in laceration of a penile artery and the formation of an arterio-cavernous fistula. It does not constitute a medical emergency in itself, and allows conservative management awaiting spontaneous resolution. Clinical case: A six-year-old boy with painless persistent erection preceded by perineal trauma. Ultrasound imaging confirmed the clinical suspicion of high flow priapism secondary to arterio-cavernous fistula. After adopting a conservative approach, the patient presented progressive detumescence, as well as ultrasound resolution one month after the episode. Comments: In high-flow priapism, venous drainage of the penis is preserved. The classical approach in adults is based on therapeutic angiography, which presents greater technical complexity and the risk of iatrogenic hypoxia in pediatric patients

Efectos colaterales de antibacilares en pacientes con enfermedad de Hansen / No disponible

Introducción: La Organización Mundial de la Salud (OMS) recomendó el uso de la poliquimioterapia (PQT) desde 1981, y desde 1998 esta pauta de tratamiento fue introducida en Paraguay. Desde ese entonces y hasta la actualidad el esquema Multibacilar (MB) comprende tres drogas: rifampicina, clofazimina y dapsona, y, el esquema Paucibacilar (PB), dos drogas: rifampicina y dapsona. Todas ellas relacionadas en mayor o menor medida a efectos colaterales. A pesar de ello, hay pocos estudios a nivel mundial, y ningún estudio en el Paraguay. Métodos: Estudio retrospectivo, observacional, de corte transversal con componente analítico, llevado a cabo en la Cátedra de Dermatología del Hospital de Clínicas - Universidad Nacional de Asunción, en San Lorenzo, Paraguay. En el periodo de enero de 2013 a octubre de 2017. Resultados: Fueron incluidos en el estudio 58 pacientes con enfermedad de Hansen, de los cuales 45 (78%) presentaron al menos un efecto colateral a la PQT, 3 pacientes presentaron más de un efecto colateral. De los 45, 25 (56%) fueron del sexo masculino y 20 (44%) del sexo femenino. En cuanto a la distribución por rango de edad: Dos (4%) en menores de 18 años, 8 (18%) de 19 a 30 años, 27 (18%) de 31 a 59 años y 8 (18%) 60 y más años. Seis (3%) pacientes de procedencia rural y 39 (87%) de procedencia urbana. Cuarenta y siete (98%) casos de efectos colaterales hematológicos (Anemia: 45; leucopenia: 1 y trombocitopenia: 1) y 1 (2%) caso de efecto colateral gastrointestinal (hepatitis). La conducta en casos de anemia: suplementación con hierro y ácido fólico: 40, suspensión de dapsona: 10 y ninguna conducta: 6 suspensión de la dapsona en 1 caso de leucopenia, suspensión de la dapsona en 1 caso de trombocitopenia y suspensión de la rifampicina en 1 caso de hepatitis. En 26 (58%) pacientes los efectos colaterales se presentaron al mes del inicio de la PQT, en 15 (33%) pacientes entre 2 y 5 meses del inicio y en 4 (9%) pacientes a los 6 y más meses del inicio. En 14 (31%) de los pacientes con efectos colaterales existía comorbilidad y en 31 (69%) casos, eran pacientes sanos. De los 45 pacientes, 41 (91%) estaban en tratamiento MB, 4 (9%) en tratamiento PB. Conclusión: La mayoría de los pacientes incluidos en el estudio presentaron efectos colaterales. Los hombres fueron los más afectados, el rango etario en el cual se presentaron con mayor frecuencia fue entre los 31 y 59 años. La mayoría procedían del medio urbano. Los efectos colaterales más frecuentes fueron los hematológicos y, de entre ellos, la anemia. Ante tal situación la medida más frecuentemente adoptada fue la suplementación con hierro y ácido fólico. En la mayoría de los casos los efectos colaterales aparecieron en el primer mes de recibir la medicación. Aquellos pacientes que recibieron PQT MB presentaron la mayor frecuencia de efectos colaterales

Introduction: The World Health Organization (WHO) recommends the implementation of multidrug (MDT) since 1981, and this régimen was introduced in Paraguay in 1998. The MDT administrate three drugs: rifampicin, clofazimine and dapsone to multibacillary patients (MB) and only two: rifampicina and dapsone to paucibacillary patients (PB). All the drugs have some adverse effects. But very few statistics have been carried out in the world on this matter and none at all in Paraguay. Methods: The work is a retrospective, observational, cross-sectional and analytical study carried out at Catedra de Dermatología del Hospital de Clínicas-Universidad Nacional de Asunción, San Lorenzo, Paraguay between January 2013 and October 2017. Results: Fifty eight leprosy patients were registered in the study and 45 (78%) presented at least one adverse effect to the MDT and 3 patients presented more tan one. 25/45 were men and 20 (44%) women. The age distributions were: Two (4%) less than 18 years old, 8 (18%) between 19-30 years old, 27(18%) 31-59 years old and 8 (18%) 60 and older. Six (3%) lived in rural setting and 39 (87%) urban. Forty seven (98%) presented adverse hematological effects (anemia: 45, leucopenia: 1 and thrombocytopenia:1) and 1 (2%) presented a gastrointestinal effect. Forty patients with anemia received iron and folic acid supplements and 6 cases with no modifications. There was 1 case leucopenia, 1 thrombocytopenia, and 1 hepatitis due to rifampicine. In 26 patients (58%) adverse effects were detected during first month of MDT, in 15 (33%) between 2-5 of treatment and in 4 (9%) patients after 6 or more months of treatment. Fourteen (31%) patients had comorbility and 31 (69%) were healthy patients. Forty one (91%) patients were receiving MB MDT and 4 (9%) PB MDT. Conclusions: The mayority of the patients in the study presented adverse effects. Men were the most affected and the mayority were in the 31-59 years age group and from urban settings. Most of the effects were hematological and among them, anemia the most frequent. These cases were supplemented with iron and folic acid. Most adverse effects appeared during the first month of treatment and MB MDT group was the most affected

Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria.

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Anomalías pulmonares congénitas y de la pared torácica / Congenital lung and chest wall malformations

El propósito de este artículo es evaluar las lesiones congénitas pulmonares y de la pared torácica que se pueden detectar desde la etapa fetal hasta alcanzar el desarrollo adulto. Nos hemos centrado en las patologías más prevalentes en ambos campos: malformaciones pulmonares congénitas aéreas (MPCA), secuestro broncopulmonar, enfisema lobar congénito, atresia bronquial y quiste broncogénico, en cuanto a las lesiones de parénquima pulmonar, y pectus excavatum, pectus carinatum, pectus arcuatum y síndrome de poland en el grupo de lesiones de pared torácica. Hemos evitado las descripciones casuísticas y las prolijas explicaciones quirúrgicas para centrarnos en la clínica y en el manejo inicial de estas malformaciones

The aim of this study was to evaluate congenital lung lesions and chest-wall deformities that can be diagnosed from the fetal period until the adulthood. We focused on the most prevalent lesions of each group: Congenital pulmonary airway Malformation (CpaM), Bronchopulmonary Sequestration, Congenital lobar emphysema, Bronchial atresia and Bronchogenic Cyst regarding to parenchymal lesions and pectus excavatum, Carinatum and poland's Syndrome in the group of wall defects. We tried to avoid series description or surgical details in order to highlight clinical issues and management decisions

Vasculitis sistémicas con compromiso cutáneo, en la Cátedra de Dermatología, Facultad de Ciencias Médicas, Universidad Nacional de Asunción / Systemic vasculitis with cutaneous involvement, in the Department of Dermatology, Faculty of Medical Sciences, National University of Asuncion

Introducción: La vasculitis sistémica presenta afectación múltiple y variada de órganos; abarca desde procesos benignos hasta mortales. Sus manifestaciones clínicas, tratamiento y pronóstico dependerán del vaso involucrado, y de la extensión y localización de la lesión. Objetivo: Determinar características epidemiológicas, clínicas, e histopatológicas, y el tratamiento de las vasculitis sistémicas con manifestaciones cutáneas en la Cátedra de Dermatología del Hospital de Clínicas, FCM - UNA. Material y método: estudio descriptivo, observacional, retrospectivo, de cohorte transversal, con componente analítico, de enero de 2004 a diciembre de 2015. Se confeccionó una planilla para registrar las variables obtenidas de fichas clínicas e histopatológicas. Resultados: Se hallaron 11 pacientes con vasculitis sistémica con afectación cutánea, (0,0098% de las consultas). Predominó el sexo masculino (63,63%). La edad media fue 30,18 años. El 18,18% eran niños todos masculinos. La lesión elemental más frecuente fue la pápula (72,72%), la localización predominante, miembros inferiores (72,72%). Los síntomas más frecuentes fueron dolor abdominal (63,63%) y la artralgia (54,54%). El 81,81% correspondía a vasculitis de vasos pequeños. En 72,72%, el componente inflamatorio eran neutrófilos. El 72,72% correspondía a Púrpura de Shönlein - Henoch (PSH), el 18,18% a Poliangeitis Microscópica (PAM), y el 9,09% a Granulomatosis con Poliangeitis (GPA). En el 72,72%, el tratamiento fue Prednisona. Conclusión: Dado que esta patología es poco frecuente, con escasos trabajos que hayan estudiado su epidemiología, este trabajo, con sus limitaciones, podría aportar para futuros estudios.

Introduction: Systemic vasculitis has multiple and varied organ involvement; Ranging from benign to deadly. Its clinical manifestations, treatment and prognosis will depend on the vessel involved, and on the extent and location of the lesion. Objectives: To determine epidemiological, clinical, and histopathological characteristics, and the treatment of systemic vasculitis with cutaneous manifestations in the Department of Dermatology Hospital of Clinics, FCM-UNA. Materials and Methods: A descriptive, observational, retrospective, cross-sectional study with an analytical component from January 2004 to December 2015. A spreadsheet was drawn up to record the variables obtained from clinical and histopathological records. Results: We found 11 patients with systemic vasculitis with cutaneous involvement, (0,0098% of the consultations). The male sex predominated (63,63%). The mean age was 30.18 years. 18,18% were children, all of them male. The most frequent elemental lesion was the papule (72,72%), the predominant location, lower limbs (72,72%). The most frequent symptoms were abdominal pain (63,63%) and arthralgia (54,54%). The 81.81% corresponded to vasculitis of small vessels. In 72,72%, the inflammatory component was neutrophils. 72,72% corresponded to Shönlein-Henoch purpura (PSH), 18,18% to Microscopic Polyangeitis (PAM), and 9,09% to Granulomatosis with Polyangeitis (GPA). In 72,72%, the treatment was Prednisone. Conclusion: Since this pathology is infrequent, with few studies that have studied its epidemiology, this work, with its limitations, could contribute for future studies.

Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study.

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR4.5 (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1IS)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1IS⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).

HPV information campaigns in Italy since 2004.

BACKGROUND: Because of its high incidence, long duration and socio-economic relevance, HPV infection can be considered a social disease, which requires the intervention of the State through appropriate communication strategies. The aim of such action is to educate people to understand, choose and implement adequate methods of prevention. METHODS: This research presents a descriptive analysis of HPV public health campaigns in Italy since the first campaign in 2004 until today. The analysis focused on the distribution of the campaigns in terms of geographical distribution and time, the target audience, the style of the message, the medium used and the prevention message. RESULTS: Forty campaigns have been identified, the most numerous of these occurring in the regions of Central and Northern Italy between 2008 and 2014. The main target was women and the most used style was the informative. The most used medium was print material. However, in 92% of cases the campaign included a web portal. Primary prevention was the main message. CONCLUSIONS: The campaigns were inadequate both in terms of time and geographical distribution. Moreover, the campaigns were addressed mostly to adult female, did not include adequately teenagers and did not include teenagers and omitted the male target, adopting ineffective communication strategies. Finally, the additional factors that may increase the risk of HPV infection and related diseases were ignored.

The impact of comorbidity on health-related quality of life in elderly patients with chronic myeloid leukemia.

The primary objective of this study was to investigate whether the presence of comorbidities was associated with a lower health-related quality of life (HRQOL) in elderly patients with chronic myeloid leukemia (CML). A sample of 174 CML patients aged 60 years or above was analyzed. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A number of pre-selected sociodemographic and disease-related factors were considered as potential confounding factors for the association between comorbidity and HRQOL. Mean age of the 174 patients analyzed was 70 years (range 60-87 years) and 55 % were male. Overall, 111 patients (64 %) reported at least one comorbidity. Analysis stratified by age group category showed a greater proportion of patients with comorbidities in the older sub-group population (≥70 years) compared to younger patients (60 to 69 years). Differences in HRQOL outcomes between patients with no comorbidity at all and those with two or more comorbid conditions were at least twice the magnitude of a clinically meaningful difference in all the physical and mental health scales of the SF-36. In multivariate analysis, after adjusting for key confounding factors, the following scales were significantly lower in those with comorbidity: general health (p < 0.001), bodily pain (p < 0.001), physical functioning (p = 0.002), and vitality (p = 0.002). Assessing comorbidity in elderly patients with CML is important to facilitate identification of those most in need of HRQOL improvements.

Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment.

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35-59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib.

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis.

We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽ 40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P = 0.04), longer survival (100% versus 96%, P = 0.05) and better combined-EFS (86% versus 71%, P = 0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients.

Differences among young adults, adults and elderly chronic myeloid leukemia patients.

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.