[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

Influence of Chemotherapy Within 30 Days Before ICU Admission on Mortality in Critically Ill Medical Patients With Cancer.

BACKGROUND: The main objective was to determine whether the administration of chemotherapy (CT) during the month before intensive care unit (ICU) admission of medical patients with cancer influences the survival rate. The design was a single-institution observational cohort study in an ICU of a tertiary university hospital. METHODS: Our cohort included 248 oncology patients admitted to the ICU from 2005 to 2014 due to nonsurgical problems. Seventy-six (30.6%) patients had received CT in the month before admission (CT group) and 172 did not receive CT (control group). The main outcome measures were ICU, hospital, 30-day, 90-day, and 1-year mortalities. We performed survival analysis using the Kaplan-Meier estimator, comparing both groups using the log-rank test, and multivariate analysis using Cox regression adjusted for gender, age, maximum Sequential Organ Failure Assessment (SOFA), and delta maximum SOFA to calculate the hazard ratios (HRs) and their respective 95% confidence intervals. This association was also evaluated by a graphic representation of survival. RESULTS: The CT group presented an ICU mortality rate of 27.6% versus 25.5% in the control group. The multivariate analysis adjusted for age, sex, and delta maximum SOFA showed significant differences between the groups (HR: 2.12; P = .009). The hospital mortality rate was 55.3% in the CT group compared to 45.4% in the control group (adjusted HR: 1.81; P = .003). At 30 days, the mortality rate was 56.6% in the CT group compared to 46.5% in the control group (adjusted HR: 1.69; P = .008). Mortality at 90 days was 65.8% in the CT group versus 59.9% in the control group (adjusted HR: 1.47; P = .03). One-year mortality was also higher in the CT group (79% vs 72.7%, adjusted HR: 1.44; P = .02). CONCLUSION: The administration of CT in the month before ICU admission in patients with cancer was associated with higher mortality in the ICU, in the hospital, and 30 and 90 days after admission when adjusted for the increase in organ failure measured by delta maximum SOFA. We provide useful new information for decision-making about ICU management of patients with cancer.

[Waldenström macroglobulinemia. Experience in 31 patients]. / Macroglobulinemia de Waldenström. Experiencia de 15 años en el Hospital del Salvador, Santiago, Chile.

BACKGROUND: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. AIM: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. PATIENTS AND METHODS: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. RESULTS: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. CONCLUSIONS: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.

[Acquired aplastic anemia during pregnancy. Report of one case]. / Aplasia medular adquirida y embarazo. Caso clínico.

Aplastic anemia (AA) or acquired aplastic anemia is an uncommon and potentially fatal disease. It is defined as reduction of at least two peripheral blood series, associated with persistent bone marrow hypocellularity. It's association with pregnancy is even more uncommon, and it may result in high mortality for the mother and the child. We report an adolescent female with aplastic anemia, which worsened during pregnancy. Her hemoglobin was 5.2 g/dl, her leukocytes were 1,833/ul and her platelets were 19,000/ul. She was initially treated with cyclosporine and horse antithymocyte globulin without hematologic improvement. At 36 weeks of pregnancy methylprednisolone and platelet transfusions were used and a cesarean section was performed. Six month later she continues to require red blood cell and platelet transfusions.

[Acquired aplastic anemia. Experience in a public hospital]. / Aplasia medular adquirida, experiencia en un hospital público de referencia.

BACKGROUND: The first line treatment for patients < 40 years old with aplastic anemia (AA) is allogeneic HLA-identical sibling donor transplantation (SCT). Immunosuppressive therapy (IST) with a combination of Thymoglobuline (ATG) and cyclosporine is used for older patients or those without a donor. Five year overall survival (OS) for both therapies is > 70%. AIM: To report the experience with SCT and ATG for AA in a public hospital. PATIENTS AND METHODS: AA was diagnosed in 42 patients between 1998 and 2016, according to Camitta criteria. Thirty eight (90%) received treatment, 7 (18%) under 40 years old received SCT, and 31 (82%) IST. The rest were not treated. OS was calculated from date of diagnosis until last control, death or loss from follow up. RESULTS: Complete or partial hematologic response, was obtained in 71% and 58% of cases with SCT and IS, respectively. Five year OS was 71% and 55% with SCT and IST, respectively. No difference in response was observed between horse and rabbit ATG. CONCLUSIONS: SCT from an HLA-identical sibling donor had a high response rate and survival. IST instead, had a lower response and survival, due to an initial high mortality rate.

ArsH from the cyanobacterium Synechocystis sp. PCC 6803 is an efficient NADPH-dependent quinone reductase.

The cyanobacterium Synechocystis sp. PCC 6803 possesses an arsenic resistance operon that encodes, among others, an ArsH protein. ArsH is a flavin mononucleotide (FMN)-containing protein of unknown function and a member of the family of NADPH-dependent FMN reductases. The nature of its final electron acceptor and the role of ArsH in the resistance to arsenic remained to be clarified. Here we have expressed and purified Synechocystis ArsH and conducted an intensive biochemical study. We present kinetic evidence supporting a quinone reductase activity for ArsH, with a preference for quinones with hydrophobic substituents. By using steady-state activity measurements, as well as stopped-flow and laser-flash photolysis kinetic analyses, it has been possible to establish the mechanism of the process and estimate the values of the kinetic constants. Although the enzyme is able to stabilize the anionic semiquinone form of the FMN, reduction of quinones involves the hydroquinone form of the flavin cofactor, and the enzymatic reaction occurs through a ping-pong-type mechanism. ArsH is able to catalyze one-electron reactions (oxygen and cytocrome c reduction), involving the FMN semiquinone form, but with lower efficiency. In addition, arsH mutants are sensitive to the oxidizing agent menadione, suggesting that ArsH plays a role in the response to oxidative stress caused by arsenite.

[Actinomycotic mycetoma due to Actinomadura madurae]. / Micetoma actinomicótico por Actinomadura madurae.

Mycetoma is a chronic, granulomatous, subcutaneous, inflammatory lesion caused by true fungi (eumycetoma) or filamentous bacteria (actinomycetoma). Mycetoma commonly affects young people between 20 and 40 years old. The most common affected site is the foot. The characteristic clinical triad is tumefaction, draining sinuses and discharging grains. We report a healthy 31-year-old male, with a 6-year history of a progressive inflammatory tumor associated with sinus tracts and granules on his left sole. Actinomycetoma was suspected. The clinical diagnosis was confirmed by microbiological and histopathological study. Polymerase chain reaction and DNA sequencing identified Actinomadura madurae. To our knowledge, this is the second case of mycetoma reported in Chile. Our report emphasizes the need to consider this diagnosis in patients with chronic granulomatous disease associated with sinus tracts, fistulas and grains.

[Susceptibility to azoles and amphotericin B of isolates of Candida spp. Experience of a university health network, between 2004 and 2010]. / Susceptibilidad a azoles y anfotericina B de aislados de Candida spp. Experiencia de una red de salud universitaria,entre 2004 y 2010.

OBJECTIVE: To describe antifungal susceptibility testing surveillance (December 2004-September 2010) in Candida spp., for amphotericin B, fluconazole and voriconazole, at the Laboratorio de Microbiología, Pontificia Universidad Católica de Chile. METHOD: The study was performed utilizing E test and included yeasts from invasive origin and isolates in which antifungal susceptibility testing was asked for by the patient's physician. RESULTS: The yeasts were mainly recovered from urine samples (n: 64), blood cultures (n: 51) and secretions (n: 24). Two hundred ninety three isolates were studied: C. albicans (38%), C. glabrata (30%), C. tropicalis (11%), C. parapsilosis (10%), C. krusei (4%) and others (7%). All Candida species were 100% susceptible to amphotericin B, except C. krusei (1/12). Fluconazole's global susceptibility in C. albicans was 91.8%, but 100% in isolates from blood cultures versus 76% in isolates from urine. C. tropicalis was 93.9% susceptible to fluconazole, C. parapsilosis, 90% and C. glabrata 30.3%. C. krusei had no susceptible isolates to fluconazole. Voriconazole resistance was mainly present in C. glabrata (11.5%). CONCLUSIONS: We recommend the study of antifungal susceptibility in isolates from invasive origin, selected urine strains and C. glabrata. Fluconazole remains effective in C. albicans from blood.

Diffuse Large B-Cell Lymphoma in Chile: The Impact of Combined CHOP Plus Rituximab in the Public Health System.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. The purpose of this study was to evaluate the clinical features, prognostic factors, and results of DLBCL that was treated in the cancer centers of the public health system in Chile and compare cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). PATIENTS AND METHODS: Patients age > 15 years who were treated in 18 cancer centers in the country between 2001 and 2017 were included. The Kaplan-Meier method was used to calculate overall survival (OS), and Cox proportional hazard regression modeling was used to evaluate the effect of the addition of rituximab to CHOP on OS. RESULTS: A total of 1,807 patients were evaluated. The median age at diagnosis was 62 (range, 15-95) years, with a female predominance (53%). Half of the patients were age ≥ 60 years. Serology for HIV infection was positive in 5% of cases (96 cases). International Prognostic Index scores were available for 90% of patients, of which 45% had low-risk, 25% low-intermediate-risk, 18% high-intermediate-risk, and 11% high-risk scores. CHOP was administered to 986 patients (55%; median follow-up, 13.2 years) and R-CHOP to 821 patients (45%; median follow-up, 8.4 years). R-CHOP was associated with superior OS compared with CHOP (5-year 66% v 48%, and 10-year 53% v 35%; P < .001). CONCLUSION: Rituximab improved the survival of patients with DLBCL diagnosed and treated in Chile. The benefit was sustained over time, with curative rates of > 50%. This intervention shows that the inclusion of this biological drug justified the expenses incurred by the Ministry of Health in the National Lymphoma Protocols in Chile.

Are the Effects of DES Over? A Tragic Lesson from the Past.

Diethylstilbestrol (DES), a transplacental endocrine-disrupting chemical, was prescribed to pregnant women for several decades. The number of women who took DES is hard to know precisely, but it has been estimated that over 10 million people have been exposed around the world. DES was classified in the year 2000 as carcinogenic to humans. The deleterious effects induced by DES are very extensive, such as abnormalities or cancers of the genital tract and breast, neurodevelopmental alterations, problems associated with socio-sexual behavior, and immune, pancreatic and cardiovascular disorders. Not only pregnant women but also their children and grandchildren have been affected. Epigenetic alterations have been detected, and intergenerational effects have been observed. More cohort follow-up studies are needed to establish if DES effects are transgenerational. Even though DES is not currently in use, its effects are still present, and families previously exposed and their later generations deserve the continuity of the research studies.

A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Patients With Diffuse Large B-Cell Lymphoma: A Study From The Latin American Group of Lymphoproliferative Disorders (GELL).

INTRODUCTION: We aimed at investigating the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in 2 independent cohorts of Latin American patients with diffuse large B-cell lymphoma (DLBCL) treated with chemoimmunotherapy. PATIENTS AND METHODS: The learning cohort was composed of 274 patients and the validation cohort of 323 patients, for a total of 597 patients. An optimal NLR cutoff ≥ 4 was determined using receiver operating characteristic analysis. RESULTS: In multivariate models, NLR ≥ 4 was independently associated with lower odds for complete response to chemoimmunotherapy in the learning (odds ratio, 0.46; P = .006) and the validation cohort (odds ratio, 0.49; P = .01), and independently associated with worse survival in the learning (hazard ratio, 1.55; P = .04) and the validation cohort (hazard ratio, 1.80; P = .003). CONCLUSIONS: The adverse prognostic value of NLR ≥ 4 was independent of the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index score. Based on the results of this multi-institutional study, NLR ≥ 4 emerges as an adverse prognostic factor in Latin American patients with DLBCL treated with chemoimmunotherapy.

Different outcomes for transplant-eligible newly diagnosed multiple myeloma patients in Latin America according to the public versus private management: a GELAMM study.

The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-.

BACKGROUND: More than 50% of patients with myelodysplastic syndromes present cytogenetic aberrations at diagnosis. Partial or complete deletion of the long arm of chromosome 5 is the most frequent abnormality. The aim of this study was to apply fluorescence in situ hybridization of 5q31 in patients diagnosed with de novo myelodysplastic syndromes in whom conventional banding cytogenetics study had shown a normal karyotype, absence of metaphases or an abnormal karyotype without evidence of del(5q). DESIGN AND METHODS: We performed fluorescence in situ hybridization of 5q31 in 716 patients, divided into two groups: group A patients (n=637) in whom the 5q deletion had not been detected at diagnosis by conventional banding cytogenetics and group B patients (n=79), in whom cytogenetic analysis had revealed the 5q deletion (positive control group). RESULTS: In group A (n=637), the 5q deletion was detected by fluorescence in situ hybridization in 38 cases (5.96%). The majority of positive cases were diagnosed as having the 5q- syndrome. The deletion was mainly observed in cases in which the cytogenetics study had shown no metaphases or an aberrant karyotype with chromosome 5 involved. In group B (n=79), the 5q deletion had been observed by cytogenetics and was confirmed to be present in all cases by fluorescence in situ hybridization of 5q31. CONCLUSIONS: Fluorescence in situ hybridization of 5q31 detected the 5q deletion in 6% of cases without clear evidence of del(5q) by conventional banding cytogenetics. We suggest that fluorescence in situ hybridization of 5q31 should be performed in cases of a suspected '5q- syndrome' and/or if the cytogenetic study shows no metaphases or an aberrant karyotype with chromosome 5 involved (no 5q- chromosome).

Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile

Background: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Aim: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. Material and Methods: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. Results: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. Conclusions: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

Epidemiology of viruses causing chronic hepatitis among populations from the Amazon Basin and related ecosystems.

On the last twenty years, viral hepatitis has emerged as a serious problem in almost all the Amerindian communities studied in the Amazon Basin and in other Amazon-related ecological systems from the North and Center of South America. Studies performed on communities from Bolivia, Brazil, Colombia, Peru and Venezuela have shown a high endemicity of the hepatitis B virus (HBV) infection all over the region, which is frequently associated to a high prevalence of infection by hepatitis D virus among the chronic HBV carriers. Circulation of both agents responds mainly to horizontal virus transmission during childhood through mechanisms that are not fully understood. By contrast, infection by hepatitis C virus (HCV), which is present in all the urban areas of South America, is still very uncommon among them. At the moment, there is not data enough to evaluate properly the true incidence that such endemicity may have on the health of the populations affected. Since viral transmission might be operated by mechanisms that could not be acting in other areas of the World, it seems essential to investigate such mechanisms and to prevent the introduction of HCV into these populations, which consequences for health could be very serious.

[Medical consultation: a practice in the 18th century]. / La consulta médica. Una práctica de la medicina en el siglo XVIII.

This paper outlines a typology of medical consultation in the 18th century, with emphasis on those carried out with the physicians present. This practice did not differ from that of previous centuries. Medical consultation, as a specifically structured procedure, served as an instrument to define the hierarchy of those present. This reflected the professional instability of the medical practice in 18th century Spain. The sources for this study include chronicles by physicians of the period that describe teh consultation sessions among doctors, gathered in what they called "Juntas", as well as written consultations.

Macroglobulinemia de Waldenström: experiencia de 15 años en el Hospital del Salvador, Santiago, Chile / Waldenström macroglobulinemia: experience in 31 patients

Background: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. Aim: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. Patients and Methods: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. Results: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. Conclusions: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.

Aplasia medular adquirida, experiencia en un hospital público de referencia / Acquired aplastic anemia: experience in a public hospital

Background: The first line treatment for patients < 40 years old with aplastic anemia (AA) is allogeneic HLA-identical sibling donor transplantation (SCT). Immunosuppressive therapy (IST) with a combination of Thymoglobuline (ATG) and cyclosporine is used for older patients or those without a donor. Five year overall survival (OS) for both therapies is > 70%. Aim: To report the experience with SCT and ATG for AA in a public hospital. Patients and Methods: AA was diagnosed in 42 patients between 1998 and 2016, according to Camitta criteria. Thirty eight (90%) received treatment, 7 (18%) under 40 years old received SCT, and 31 (82%) IST. The rest were not treated. OS was calculated from date of diagnosis until last control, death or loss from follow up. Results: Complete or partial hematologic response, was obtained in 71% and 58% of cases with SCT and IS, respectively. Five year OS was 71% and 55% with SCT and IST, respectively. No difference in response was observed between horse and rabbit ATG. Conclusions: SCT from an HLA-identical sibling donor had a high response rate and survival. IST instead, had a lower response and survival, due to an initial high mortality rate.

Selegiline (deprenyl) decreases calbindin-D28k expression in cortical neurons of rats socially deprived during the post-weaning period.

Preclinical studies indicate that selegiline (deprenyl), frequently used in some neurodegenerative diseases, exert protective effects on central nervous system neurons of individuals exposed to social isolation (SI). Furthermore, it has been suggested that SI produces neuronal dysfunction due in part to an excessive intracellular Ca(2+) overload. Since the main intracellular Ca(2+) buffering mechanism involves changes in the calcium-binding protein calbindin-D28k (CB), and that CB neuronal expression can increase in response to Ca(2+) transients, we hypothesized that chronic selegiline administration in early socially isolated animals could minimize cell CB expression as an indirect indicator of protective mechanism against Ca(2+) overload. In the present study male rats were weaned at postnatal day 21 (P21) and randomly assigned to social deprivation (SI) or control (SC) environments for 30 days (P21-51). SI animals were further subdivided in two experimental groups: socially deprived-saline (SI-SAL) and socially isolated-selegiline (SI-SEL) for additional 30 days (P52-82). Medial frontal CB immunoreactivity (CB-ir) neurons were quantitatively and qualitatively analyzed. The results obtained indicate that neocortical cells of adult rats submitted to early SI show a significant increase in the number of CB-ir neurons per cortical field, while selegiline treatment significantly reduces this parameter.