[Nystagmus secondary to albinism with ocular involvement in a female: A diagnostic challenge]. / Nistagmo secundario a albinismo con compromiso ocular en paciente femenina: Un desafío diagnóstico.

INTRODUCTION: Infantile nystagmus is an infrequent condition that represents a diagnostic challenge for the pediatri cian. Albinism is one of its main causes, being difficult to suspect in the absence of evident cutaneous involvement, especially in female patients, due to the inheritance type of ocular albinism. Objec tive: To describe a case of nystagmus secondary to albinism with isolated ocular involvement in a female patient, in order to provide tools for pediatric approach and diagnosis. CLINICAL CASE: Three- weeks-old female patient, without morbid history, referred to a pediatric neurosurgeon and ophthal mologist due to paroxysmal eye movements since 2 weeks of age. The electroencephalogram and brain images were normal. In follow-up monitoring at 3 months, iris translucency, nystagmus, and hypermetropic astigmatism were confirmed. Dermatologic evaluation ruled out cutaneous invol vement. The patient developed cephalic downward inclination and coordination development de lay was confirmed, the patient was handled with corrective lenses and kinesiotherapy. In follow-up monitoring at 3 years, there was an improvement in visual acuity, decreased nystagmus and normal neurodevelopment. The ophthalmological evaluation of both parents was normal and there was no history of nystagmus or albinism in the family. Upon her parents' decision, no genetic study was ca rried out. CONCLUSION: The diagnosis of nystagmus secondary to ocular albinism, even in the absence of cutaneous involvement, is clinical. The genetic study allows confirming the etiology, without being an essential examination, unless family planning is considered. Timely research and multidisciplinary intervention determine a better prognosis.

[Rett Syndrome: MECP2 gene molecular analysis in Chilean patients]. / Síndrome de Rett: Análisis molecular del gen MECP2 en pacientes chilenas.

INTRODUCTION: Rett syndrome (RTT) is a progressive neurological disorder characterized by regres sion of psychomotor development in previously healthy girls. Most cases are due to pathogenic va riants in the MECP2 gene which encodes for the methyl CpG-binding protein 2. OBJECTIVE: To des cribe the frequency and type of pathogenic variants in the MECP2 gene in Chilean female patients with clinical diagnosis of RTT. PATIENTS AND METHOD: Chilean women with clinical suspicion of RTT were invited to participate in the study. Clinical data were collected through a questionnaire. MECP2 pathogenic variants were analyzed by Sanger sequencing method and Multiplex Ligation-dependent Probe Amplification (MLPA) was used to detect duplications or deletions. RESULTS: The study in cluded 14 patients with suspected RTT, of which eight (57%) patients had pathogenic variants. The other patients remain without molecular diagnosis. CONCLUSIONS: Pathogenic variants in MECP2 are present in Chilean patients with RTT. It is likely that there are other genes or diagnoses involved in patients without MECP2 findings. As of this study, molecular diagnosis is available in Chile.

[CFTR gene sequencing in a group of Chilean patients with cystic fibrosis]. / Secuenciación del gen CFTR en un grupo de pacientes chilenos con fibrosis quística.

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations of the CFTR gene, in which over 1,900 different mutations have been identified. In Chile, the diagnosis panel with the 36 most common mutations detects approximately 50% of all alleles, while for Caucasians, it is nearly 90%. The objective of this study is to expand the capacity of mutational screening in Chilean patients and look for recurrent mutations at the national level. METHOD: The detection of unknown pathogenic alleles was assessed by CFTR gene sequencing in a selected group of patients from the National Cystic Fibrosis Foundation (NCFF). 39 patients, who met the CF diagnostic criteria and had only one allele identified according to the mutational panel, were studied. Massive sequencing was performed throughout the investigation and the main CFTR databases were used for analysis. RESULTS: The second pathogenic allele was identified in 16 of 39 patients of this study (41%), finding eleven different mutations that had not been reported in our population. We believe that the reason is that one of the variants had not been previously described. CONCLUSIONS: Mutations that had been described mainly in Hispanic and/or Mediterranean populations were identified. We found a variation that had not been previously reported, but not enough recurrent mutations that could explain the low rate of detection were found. Knowledge about mutations can provide appropriate genetic counseling and will be critical to evaluate the potential use of new targeted therapies for treating them.

Physicians' age and sex influence breaking bad news to elderly cancer patients. Beliefs and practices of 50 Italian oncologists: the G.I.O.Ger study.

PURPOSE: We attempt to shed light on the truth-telling attitudes and practices of oncologists working with a geriatric population in Italy. PARTICIPANTS AND METHOD: Physicians caring for cancer patients were asked to complete a specific survey centred on their beliefs, attitudes and practices towards truth telling to elderly cancer patients. RESULTS: Of 50 physicians surveyed, 68% were men. Physicians practising in the south of Italy were significantly older and more likely to be of male gender in comparison with physicians practising from the north and central areas. Eighty-four per cent of physicians consider the family to be an obstacle to a direct communication with the elderly. Forty-four per cent of male physicians who are faced with a family's request of nondisclosure talk with the patient, whereas 37.5% of female physicians talk with the family. For 60% of interviewed physicians, the reason underpinning the caregiver's choice of nondisclosure is to delay the emotional confrontation. CONCLUSIONS: We observed that variability of disclosure is related not only to the patient's age but also to the physicians' age and sex and to the geographic area where physicians work. The results also show that both caregivers and physicians are concerned by the emotional aspects related to clinical information. Italian oncologists have to learn and implement 'comprehensive' communication skills and have to promote an integration of the information needs of patient and caregivers, according to their socio-cultural affiliation, within the communication techniques.

First Report of Verticillium Wilt caused by Verticillium dahliae Kleb. on New Zealand Spinach (Tetragonia tetragonioides) in Italy.

Tetragonia tetragonioides (New Zealand spinach, Aizoaceae) is an Australasian annual species that occurs naturally in Italy, where it is cultivated for the edible young shoots and succulent leaves. In September 2011, a previously unknown wilt was observed in 10 private gardens, each 0.1 to 0.5 ha, near Castellaro, Northern Italy, on 7-month-old New Zealand spinach plants. Leaves wilted, starting from the collar and moving up the plant, and vascular tissues showed brown streaks in the roots, crowns, and stems. Diseased plants were stunted with small, chlorotic leaves. Infected stems and leaves then wilted, and plants often died. Of about 500 plants, 30% were affected. Stems of 10 diseased plants were disinfected with 1% NaOCl for 1 min. Sections of symptomatic vascular tissue were plated on potato dextrose agar. After 3 days at 23 ± 1°C, colonies developed that were white and turned a grey to dark green color. Irregular, black microsclerotia (32.0) 63.1 ± 16.8 µm (106.1) × (18.7) 39.1 ± 12.3 µm (65.8) developed in hyaline hyphae after 8 days. Hyaline, elliptical, single-celled conidia (2.7) 3.8 ± 0.6 µm (4.8) × (1.9) 2.6 ± 0.5 µm (3.5) developed on verticillate conidiophores with three phialides at each node. Based on these morphological characteristics, the fungus was identified as Verticillium dahliae (1). The internal transcribed spacer (ITS) region of rDNA was amplified for one isolate using the primers ITS1/ITS4 (3) and sequenced (GenBank Accession No. JX308315). BLASTn analysis of the 479-bp segment showed 100% homology with the ITS sequence of a V. dahliae isolate (AB551206). Pathogenicity tests were performed twice using 60-day-old plants of T. tetragonioides. Unwounded roots of eight plants were dipped for 1 min in a conidial suspension (5 × 107 conidia/ml) of one isolate of V. dahliae obtained from the original infected New Zealand spinach plants, and grown in potato dextrose broth. The inoculated plants were transplanted into 2-liter pots (1 plant/pot) containing steamed potting mix (sphagnum peat-perlite-pine bark-clay; 50:20:20:10) and maintained in a growth chamber at 20 to 24°C and 50 to 80% RH. Eight plants immersed in sterile water served as a control treatment. Wilt symptoms were observed 30 days after inoculation, with vascular discoloration in the roots, crowns and stems. V. dahliae was reisolated consistently from infected tissues, but not from the control plants that remained healthy. Pathogenicity was also tested using the same method on plants of four cultivars (five plants/cultivar) of Spinacia oleracea (Matador, Asti, Merlo Nero, and America). Wilt symptoms developed on all cultivars and V. dahliae was reisolated from each inoculated plant. No fungal colonies were reisolated from control plants, which remained healthy. To our knowledge, this is the first report of Verticillium wilt caused by V. dahliae on T. tetragonioides in Italy, as well in Europe. V. dahliae was reported on T. tetragonioides in Canada (2). At this time, the economic impact of Verticillium wilt on New Zealand Spinach in Italy is limited, although the use of this vegetable in Italy is increasing. References: (1) G. F. Pegg and B. L. Brady. Verticillium Wilts. CABI Publishing, Wallingford, UK, 2002. (2) M. J. Richardson. Page 387 in: An Annotated List of Seed-Borne Diseases, Fourth Edition. International Seed Testing Association, Zurich, Switzerland, 1990. (3) T. J. White et al. Page 315 in: PCR Protocols. A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.

Golovinomyces biocellatus on Oregano (Origanum vulgare 'Compactum') in Italy.

Origanum vulgare L., common name oregano, also known as pot marjoram, Lamiaceae family, is grown for its aromatic and medicinal properties and as an ornamental. In particular, O. vulgare 'Compactum' is becoming popular as a potted plant. During January 2011, 3-month-old plants grown on a commercial farm located near Albenga (northern Italy) showed signs and symptoms of an unknown powdery mildew. Ninety percent of the plants were affected. The adaxial leaf surfaces were covered with white mycelia and conidia, while the abaxial surfaces were less infected. As the disease progressed, infected leaves turned yellow, wilted, and eventually fell off. Mycelia were also observed on stems. Conidia were hyaline, elliptical, borne single or in short chains (three to four conidia per chain), and measured 37.9 × 19.6 (31.2 to 45.1 × 14.9 to 26.2) µm. Conidiophores were erect with a cylindrical foot cell measuring 81.1 × 9.7 (54.2 to 112.4 × 7.9 to 11.6) µm followed by two to three shorter cells measuring 26.8 × 11.8 (16.6 to 38.1 × 8.5 to 15.3) µm. Fibrosin bodies were absent. Chasmothecia were not observed in the collected samples. The internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1F/ITS4 and sequenced (3) (GenBank Accession No. JN594608). The 560-bp amplicon had 99% homology with the sequence of Golovinomyces biocellatus (GenBank Accession No. AB307675). Pathogenicity was confirmed through inoculation by spraying a conidial suspension (6 × 104 CFU/ml) prepared from diseased leaves onto leaves of healthy O. vulgare 'Compactum' plants. Four plants were inoculated while the same number of noninoculated plants served as a control. Plants were maintained in a glasshouse at temperatures ranging from 23 to 28°C. Ten days after inoculation, typical symptoms of powdery mildew developed on inoculated plants. The fungus observed on inoculated plants was morphologically identical to that originally observed. Noninoculated plants did not show symptoms. The pathogenicity test was carried out twice. G. biocellatus on O. vulgare has been reported in Switzerland (2) and Argentina (4) and it is present on other plant genera in Italy. In Italy, on the same host, attacks of Erysiphe galeopsis have been previously reported (1). The economic importance of this disease is currently limited due to limited planting of this species. However, in the last years, potted aromatic plants represent a steady increasing crop in Italy. Voucher specimens are available at the Agroinnova Collection, University of Torino. References: (1) K. Amano. Host Range and Geographical Distribution of the Powdery Mildew Fungi. Japan Science Society Press, Tokyo, 1986. (2) A. Bolay. Cryptog. Helv. 20:1, 2005. (3) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990. (4) S. M. Wolcan. J. Plant Patho. 91:501, 2009.

First Report of Fusarium oxysporum Causing Wilt on Iceland Poppy (Papaver nudicaule) in Italy.

During fall 2011, symptoms of a wilt disease were observed in a commercial nursery near Ventimiglia as well as in the Research Center of Floriculture of Sanremo (northern Italy) on plants of Papaver nudicaule (Iceland poppy) of a local unnamed cultivar. In the commercial nursery, 15 to 20% of plants were affected, while about 3% of plants were affected at the Research Center. Symptoms consisted of chlorosis, premature leaf drop, and foliar wilting, followed by the stem wilting, bending, and eventually rotting from the base. Brown discoloration was observed in the stem vascular tissue. Using Komada's Fusarium-selective agar medium (2), a fungus was consistently and readily isolated from symptomatic vascular tissue of plants collected from both sites. The isolates were purified and subcultured on potato dextrose agar (PDA), on which medium both isolates produced pale violet, abundant, aerial mycelium, felted in old cultures, with pale purple pigments in the agar medium. The isolate generated short monophialides with unicellular, ovoid-elliptical microconidia of 3.9 to 6.7 × 1.4 to 3.0 (average 5.4 × 2.3) µm. On carnation leaf agar (CLA) (1), isolates produced pale orange sporodochia with macroconidia that were 3-septate, slightly falcate with a foot-shaped basal cell and a short apical cell, and 26.0 to 43.5 × 3.1 to 4.4 (average 35.3 × 3.7) µm. Chlamydospores were abundant, terminal, and intercalary, rough walled, mostly singles but sometime in short chains or clusters, and 5.2 to 10.1 µm in diameter. Such characteristics are typical of Fusarium oxysporum (3). The internal transcribed spacer (ITS) region of rDNA was amplified from the isolates using the primers ITS1/ITS4 (4), and sequenced. BLASTn analysis of the 507-bp ITS sequence of one isolate from P. nudicaule collected from the commercial nursery (GenBank Accession No. JX103564) showed an E-value of 0.0 and 100% identity with the ITS sequence of F. oxysporum (HQ649820). To confirm pathogenicity of one of the Iceland poppy isolates, tests were conducted on 2-month-old plants of the same cultivar on which symptoms were first observed. Plants (n = 14) were inoculated by dipping roots in a 1 × 107 CFU/ml conidial suspension of the isolate of F. oxysporum prepared from 10-day-old cultures grown in potato dextrose broth (PDB) on a shaker (90 rpm) for 10 days at 22 ± 1°C (12-h fluorescent light, 12-h dark). Non-inoculated control plants (n = 14) were dipped in sterilized water. All the plants were transplanted into pots filled with steamed potting mix (sphagnum peat/perlite/pine bark/clay at 50:20:20:10), and maintained in a glasshouse at 24 to 28°C. Inoculated plants showed typical symptoms of Fusarium wilt after 10 days. The stems then wilted and plants died. Non-inoculated plants remained healthy. F. oxysporum was reisolated from inoculated plants but not from control plants. The pathogenicity test was conducted twice with the same results. Since Fusarium wilt has not previously been described on Iceland poppy at any location, this is first report of F. oxysporum on P. nudicaule in Italy and anywhere in the world. References: (1) N. L. Fisher et al. Phytopathology 72:151, 1982. (2) H. Komada. Rev. Plant Prot. Res. 8:114, 1975. (3) J. F. Leslie and B.A. Summerell. The Fusarium Laboratory Manual, Blackwell Professional, IA, 2006. (4) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, CA, 1990.

EORTC workshop on clinical trial methodology in older individuals with a diagnosis of solid tumors.

BACKGROUND: Due to the aging of the population, the number of older patients diagnosed with a malignant disease is increasing. A multidisciplinary approach to the senior adult cancer patient is mandatory, to assure optimal diagnosis and therapeutic management. DESIGN: European Organisation for Research and Treatment of Cancer (EORTC) has currently defined senior adult oncology as one of its priorities and has established an active Elderly Task Force (ETF). Under the auspices of the EORTC, the ETF organized a workshop on clinical trial methodology in older cancer patients and in this article, we present the conclusions of this workshop. RESULTS: Besides the 'classical' efficacy end points, quality of life, functional status and independence of the patient should be assessed in clinical trials in older patients. The participants of the workshop agreed on the use of a minimum dataset for the assessment of global health and functional status in older cancer patients. The panel also recommended that optimization of collaboration with pharmaceutical industry requires reporting of age-related data (subgroup analyses of clinical trials, age-related pooled analyses and obligatory post-marketing studies in vulnerable and frail older patients). CONCLUSION: The identification of proper clinical outcomes and the validation of geriatric screening tools are needed for conducting sound and comparable clinical trials.

DNA-functionalized solid state nanopore for biosensing.

The possible use of nanopores for single DNA molecules biosensing has been demonstrated, but much remains to do in order to develop advanced engineered devices with enhanced stability, and controlled geometry and surface properties. Here we present morphological and electrical characterization of solid state silicon nitride nanopores fabricated by focused ion beam direct milling and chemically functionalized by probe oligonucleotides, with the final aim of developing a versatile tool for biosensing and gene expression profiling.

[Sociodemographic risk factors of hantavirus cardiopulmonary syndrome]. / Factores de riesgo socio-demográficos del síndrome cardiopulmonar por hantavirus.

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) is caused by new world hantaviruses, among which Andes hantavirus (ANDV) is endemic to Chile and Southern Argentina. The disease caused by ANDV produces plasma leakage leading to enhanced vascular permeability and has a high case fatality rate (35%), mainly due to respiratory failure, pulmonary edema and myocardial dysfunction, hypoperfusion and shock. Host sociodemographic and genetic factors might influence the course and outcome of the disease. Yet, they have not been thoroughly characterized. AIM: To evaluate sociodemographic factors as risk factors in severity of HCPS. PATIENTS AND METHODS: Study period: 2004-20013, attending in eight collaborative centers, etiological diagnosis was performed by serology or molecular biology, mild and severe HCPS were compared.139 Chilean patients were analyzed, 64 (46%) with severe disease among which 12 (19 %) died. RESULTS: European ethnicity had 5,1 times higher risk than Amerindian ethnic group to develop a severe HCPS, greater seriousness that was also associated with an urban residence. CONCLUSION: It was observed that ethnicity and type of residence were significant risk factors for HCPS severity. Hypotheses explaining these findings are discussed.

EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update.

Anaemia is frequently diagnosed in patients with cancer, and may have a detrimental effect on quality of life (QoL). We previously conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer 2004;40:2201-2216.] We report here an update to these guidelines, including literature published through to November 2005. The results of this updated systematic literature review have enabled us to refine our guidelines based on the full body of data currently available. Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, and in patients undergoing cancer surgery. The addition of further Level I studies confirms our recommendation that in cancer patients receiving chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 9-11 g/dL based on anaemia-related symptoms rather than a fixed Hb concentration. Early intervention with erythropoietic proteins may be considered in asymptomatic anaemic patients with Hb levels 11.9 g/dL provided that individual factors like intensity and expected duration of chemotherapy are considered. Patients whose Hb level is below 9 g/dL should primarily be evaluated for need of transfusions potentially followed by the application of erythropoietic proteins. We do not recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy or radiotherapy who have normal Hb levels at the start of treatment, as the literature has not shown a benefit with this approach. The addition of further supporting studies confirms our recommendation that the target Hb concentration following treatment with erythropoietic proteins should be 12-13 g/dL. Once this level is achieved, maintenance doses should be titrated individually. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia, with studies supporting the use of epoetin alfa and epoetin beta weekly and darbepoetin alfa given every week or every 3 weeks. We do not recommend the use of higher than standard initial doses of erythropoietic proteins with the aim of producing higher haematological responses, due to the limited body of evidence available. There is Level I evidence that, within reasonable limits of body weight, fixed doses of erythropoietic proteins can be used to treat patients with chemotherapy-induced anaemia. This analysis confirms that there are no baseline predictive factors of response to erythropoietic proteins that can be routinely used in clinical practice if functional iron deficiency or vitamin deficiency is ruled out; a low serum erythropoietin (EPO) level (only in haematological malignancies) appears to be the only predictive factor to be verified in Level I studies. Further studies are needed to investigate the value of hepcidin, c-reactive protein, and other measures as predictive factors. In these updated guidelines, we explored a new question of whether oral or intravenous iron supplementation increases the response rate to erythropoietic proteins. We found no evidence of increased response with the addition of oral iron supplementation, but there is Level II evidence of improved response to erythropoietic proteins with the addition of intravenous iron. However, the doses and schedules for intravenous iron supplementation are not yet well defined, and further studies in this area are warranted. The two major goals of erythropoietic protein therapy are prevention or elimination of transfusions and improvement of QoL. The total body of evidence shows that red blood cell (RBC) transfusion requirements are reduced following treatment with erythropoietic proteins. This analysis also confirms that QoL is significantly improved in patients with chemotherapy-induced anaemia and in those with anaemia of chronic disease following erythropoietic protein therapy, with more robust evidence now available that QoL was improved in studies investigating early intervention in cases of chemotherapy- or radiotherapy-induced anaemia. There is only indirect evidence that patients with chemotherapy-induced anaemia or anaemia of chronic disease initially classified as non-responders to standard doses proceed to respond to treatment following a dose increase. None of the studies addressed the question in a prospective, randomised fashion, and so the Taskforce does not recommend dose escalation as a general approach in all patients who are not responding. There is still insufficient data to determine the effect on survival following treatment with erythropoietic proteins in conjunction with chemotherapy or radiotherapy. Our analysis of survival endpoints in studies involving patients receiving radio(chemo)therapy found that most studies were inconclusive, with no clear link between the use of erythropoietic proteins and survival. Likewise, we found no clear link between erythropoietic therapy and other endpoints such as local tumour control, time to progression, and progression-free survival. There is no evidence that pure red cell aplasia occurs in cancer patients following treatment with erythropoietic proteins, and the fear of this condition developing should not lead to erythropoietic proteins being withheld in patients with cancer. There is Level I evidence that the risk of thromboembolic events and hypertension are slightly elevated in patients with chemotherapy-induced anaemia receiving erythropoietic proteins. Additional trials are warranted, especially to define the optimal doses and schedules of intravenous iron supplementation during erythropoietic therapy. While our review did not address cost benefit evaluations in detail, the consensus is that studies taking into account all real determinants of cost and benefit need to be performed prospectively.

Tendencia de la mortalidad por fibrosis quística en Chile, 1997-2017 / Cystic fibrosis mortality trend in chile, 1997-2017

Introducción. La Fibrosis Quística es la enfermedad hereditaria con pronóstico reducido más frecuente en raza blanca. Su incidencia varía según etnias. En Chile, la incidencia estimada es de 1/10.000 habitantes y la evidencia nacional acerca de la magnitud y caracterización de defunciones es escasa. El objetivo de este estudio es determinar la evolución de mortalidad por fibrosis quística en Chile durante 1997-2017. Materiales y Métodos. Estudio descriptivo retrospectivo sobre la tendencia de mortalidad por fibrosis quística en Chile. A partir de bases de datos secundarias del sistema de estadísticas de mortalidad del país, se analizó la cohorte de fallecidos registrado en el certificado de defunción como fibrosis quística. Se calcularon tasas de mortalidad crudas y ajustadas para todos los años observados. Se realizó un análisis para las defunciones en menores 40 años; según las variables sexo, edad y región. Se estimó el cambio porcentual anual utilizando el programa Joinpoint-Regression. Resultados. Se registraron 198 defunciones (49% mujeres). La edad media y mediana de defunción aumentaron progresivamente, desde 1997-2001 con media 8,5 y mediana 6 años a 2013-2017 con media 19,6 y mediana 20 años (p-valor<0,05). La tasa de mortalidad en los menores de 1 año presentó una tendencia decreciente con un cambio porcentual anual de - 32,5%, estadísticamente significativo. La región de Atacama presentó un riesgo de muerte 6,12 veces mayor que el promedio del país. Discusión. En Chile, la edad de defunción por fibrosis quística ha aumentado progresivamente y la mortalidad en los <1 año ha disminuido a lo largo de los últimos años.

Introduction. Cystic Fibrosis is the most frequent hereditary disease in whites, with a reduced prognosis. Its incidence varies by ethnicity. In Chile, the estimated incidence is 1/10,000 inha-bitants and national evidence regarding the magnitude and characterization of deaths is scarce.The aim of this study es to describe the evolution of cystic fibrosis mortality in Chile during 1997-2017. Materials and Methods. Retrospective descriptive study on the mortality trend due to cystic fibrosis in Chile. From secondary databases of the country's mortality statistics system, the cohort of deceased due to cystic fibrosis, as registered in the death certificate was analyzed. Crude and adjusted mortality rates were calculated for all observed years. An analysis was performed for deaths in persons younger 40 years; according to the variables of sex, age and region. The annual percentage change was estimated using the Joinpoint-Regression program.Results. 198 deaths were registered (49% women). For those younger than 40 years at the time of death, the mean and median age of death increased progressively, from mean 8.5 and median 6 years in 1997 to 2001 to a mean of 19.6 and median of 20 years in 2013-2017 (p-value <0.05). The mortality rate in under 1 year of ages presented a decreasing trend with an annual percentage change of -32.5%. The Atacama region presented a risk of death 6.12 times higher than the country's average.Discussion. In Chile, the age of death due to cystic fibrosis has progressively increased and mortality in <1 year has decreased in recent years

Testicular germ cell tumors and human immunodeficiency virus infection: a report of 26 cases. Italian Cooperative Group on AIDS and Tumors.

PURPOSE: Besides tumors that are diagnostic of AIDS, such as non-Hodgkin's lymphoma, Kaposi's sarcoma, and invasive carcinoma of the cervix, other tumors have been described in the human immunodeficiency virus (HIV) setting. Some case reports on testicular cancer in HIV-infected patients have appeared in the literature. We present a retrospective study on 26 cases of testicular germ cell tumors (TGCTs) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT) between November 1986 and September 1994. PATIENTS AND METHODS: Twenty-six patients with TGCT and HIV-infection from the GICAT were retrospectively analyzed. RESULTS: Fourteen patients had seminoma and 12 had nonseminoma. Four patients underwent only orchidectomy, one patient received only chemotherapy, nine patients were treated with postsurgical chemotherapy, 10 patients (38%) received postsurgical radiotherapy, one patient received postsurgical chemotherapy plus radiotherapy, and one patient was lost for follow-up evaluation immediately after diagnosis. The complete response (CR) rate was 95%. Relapse occurred in 32% of patients. The median follow-up time was 33 months. The mortality rate was 37%. Causes of death were neoplasia in three of nine patients, AIDS in five of nine patients, and fortuitous event in one of nine patients. The overall 3-year survival rate was 65%, and the 3-year disease-free survival rate was 65%. Severe hematologic toxicity was observed in seven of 15 patients. CONCLUSION: HIV-infected patients with testicular cancer should be offered standard oncologic therapy, irrespective of their HIV status, since the majority can be cured of their tumor and have a good quality of life. Use of concomitant prophylaxis for opportunistic infections is recommended.

Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer.

Fifty-two previously untreated patients with small-cell lung carcinoma (SCLC) were treated with a combination of carboplatin 300 mg/m2 intravenously (IV) on day 1 and etoposide 100 mg/m2 IV on days 1 through 3 every 28 days for four courses. Patients with limited disease (LD) subsequently received thoracic radiotherapy; no prophylactic cranial radiotherapy was used. Forty-four patients (85%) achieved an objective response, including 82% (29% complete remissions) of LD patients and 88% (13% complete remissions) of extensive-disease (ED) patients. Median response duration for LD patients was 7 months and 5.5 months for ED patients. Median survival for both LD and ED patients was 9.5 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3/4 leucopenia occurring in 44% of patients. There was one (2%) treatment-related neutropenic death. Treatment was otherwise well tolerated, and in particular no renal toxicity, neurotoxicity, or ototoxicity was seen. This new combination is highly active in terms of response rate, but response duration and survival is disappointing, and might be improved by prolonged treatment or by the use of additional drugs in combination.

Nistagmo secundario a albinismo con compromiso ocular en paciente femenina: un desafío diagnóstico / Nystagmus secondary to albinism with ocular involvement in a female: a diagnostic challenge

INTRODUCCIÓN: El nistagmo infantil es infrecuente y representa un desafío diagnóstico para el pediatra. El albinismo es una de sus principales causas, siendo difícil de sospechar en ausencia de compromiso cutáneo evidente, especialmente en pacientes femeninas, debido a que tipo de herencia del albinismo ocular. OBJETIVO: Describir un caso de nistagmo secundario a albinismo con compromiso ocular aislado en paciente femenina, para discutir el enfoque diagnóstico pediátrico. CASO CLÍNICO: Paciente fe menino de 3 semanas de vida, sin antecedentes mórbidos, derivada a neuropediatra y oftalmólogo por movimientos oculares paroxísticos desde las 2 semanas, con estudio con electroencefalograma e imágenes cerebrales normales. A los 3 meses se confirmó translucencia iridiana, nistagmo y astigmatismo hipermetrópico. La valuación dermatológica descartó compromiso cutáneo. Evolucionó con inclinación cefálica hacia abajo y retraso del desarrollo de la coordinación, fue manejada con lentes de corrección y kinesioterapia. A los 3 años, destacaba mejoría de la agudeza visual, disminución del nistagmo y neurodesarrollo normal. La evaluación oftalmológica de ambos padres fue normal y no había antecedentes de nistagmo o albinismo en la familia. Por decisión de los padres no se realizó estudio genético. CONCLUSIÓN: El diagnóstico de nistagmo secundario a compromiso ocular del albinismo, aún en ausencia de afección cutánea, es clínico; el estudio genético permite confirmar la etiología, sin ser un examen imprescindible, a menos que se considere la planificación familiar. La pesquisa oportuna e intervención multidisciplinaria determinan un mejor pronóstico.

INTRODUCTION: Infantile nystagmus is an infrequent condition that represents a diagnostic challenge for the pediatri cian. Albinism is one of its main causes, being difficult to suspect in the absence of evident cutaneous involvement, especially in female patients, due to the inheritance type of ocular albinism. OBJECTIVE: To describe a case of nystagmus secondary to albinism with isolated ocular involvement in a female patient, in order to provide tools for pediatric approach and diagnosis. CLINICAL CASE: Three- weeks-old female patient, without morbid history, referred to a pediatric neurosurgeon and ophthal mologist due to paroxysmal eye movements since 2 weeks of age. The electroencephalogram and brain images were normal. In follow-up monitoring at 3 months, iris translucency, nystagmus, and hypermetropic astigmatism were confirmed. Dermatologic evaluation ruled out cutaneous invol vement. The patient developed cephalic downward inclination and coordination development de lay was confirmed, the patient was handled with corrective lenses and kinesiotherapy. In follow-up monitoring at 3 years, there was an improvement in visual acuity, decreased nystagmus and normal neurodevelopment. The ophthalmological evaluation of both parents was normal and there was no history of nystagmus or albinism in the family. Upon her parents' decision, no genetic study was ca rried out. CONCLUSION: The diagnosis of nystagmus secondary to ocular albinism, even in the absence of cutaneous involvement, is clinical. The genetic study allows confirming the etiology, without being an essential examination, unless family planning is considered. Timely research and multidisciplinary intervention determine a better prognosis.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística

Resumen La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística / Chilean consensus for the integral care of children and adults with cystic fibrosis

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Cancer in the elderly: assessing patients for fitness.

As aging is highly heterogeneous, the clinical evaluation of the older person with cancer is influenced by several factors including comorbid conditions, disabilities, tumour type and stage. Assessment of comorbidity and disability represent on evolving area of research. Results from geriatrics are now translating in clinical oncology. Instruments for measurement of comorbidity and disability have been evaluated in the older cancer patients with promising results. The use of comprehensive geriatric assessment (CGA) in the older cancer patient represents a major improvement in the oncological practice. CGA is based on standardised interviews and covers areas of physical and psychical dysfunction. Moreover, CGA allows the collections of homogeneous information among different centres and recognition of the frail elderly. A diffuse ageistic prejudice may prevent adequate evaluation and treatment of older individuals. A wide based educational effort may allow a more appropriate management of the older cancer patient.

Life expectancy, comorbidity and quality of life: the treatment equation in the older cancer patients.

With ageing, function preservation and maintenance of quality of life represent a major goal in an increasing proportion of patients. Life expectancy is a function of age, comorbidity, disability and cancer type and stage. Decision-making involves a delicate balance among all these factors, evaluation of treatment related complications of the overall effects of cancer and cancer treatment on the patients' quality of life. Despite several instruments for the assessment of quality of life being validated, none have been calibrated to the special requirements of the older patients. The structured interview administered by a trained clinician represents a standard approach for geriatric research and even for clinical practice because of the frailty of the older population. The combination of this approach with the self-administered questionnaire appears the most effective way to minimise missing data in collecting information for patients unable to complete the form.