Estudio descriptivo de la amiloidosis por transtiretina en un hospital de tercer nivel sin unidad de referencia / A descriptive study of transthyretin amyloidosis in a tertiary hospital without a referral unit

Antecedentes y objetivo: La amiloidosis por transtiretina (ATTR) es una enfermedad rara que forma parte de las amiloidosis sistémicas, y es una enfermedad amenazante para la vida. Puede afectar a todos los órganos y sistemas, siendo la más frecuente la afectación neurológica y cardíaca. El objetivo de este estudio es detectar posibles casos de ATTR y realizar un estudio descriptivo de los mismos. Material y métodos: Estudio descriptivo unicéntrico realizado en un hospital de tercer nivel en el que se incluyen pacientes con sospecha de ATTR entre septiembre de 2016 y enero de 2020. Resultados: Se detectan 190 pacientes sospechosos de ATTR. En el estudio se incluyen 100 de ellos, así como 10 familiares de pacientes en los que se detecta ATTR en su variante genética. En total, se detecta ATTR variante genética en 7 individuos (3 con mutación presintomática de la enfermedad), 16 pacientes con ATTR asociada a la edad y 31 individuos con amiloidosis cardíaca no filiada con las pruebas realizadas, lo que confirma la presencia de esta enfermedad en áreas no endémicas. Conclusiones: La ATTR es una enfermedad que se ha de tener en cuenta en el diagnóstico diferencial de pacientes que presentan insuficiencia cardíaca con FEVI preservada, principalmente si se asocia a síntomas neurológicos (AU)

Background and objective: Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them. Material and methods: Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020. Results: A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas. Conclusions: ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms (AU)

Venous thromboembolism incidence in cancer patients with germline BRCA mutations

BackgroundGermline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown.Materials and methodsWe performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Marañón, Spain, from 2010 to 2019.ResultsOne-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients.ConclusionsThe VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.

A descriptive study of transthyretin amyloidosis in a tertiary hospital without a referral unit.

BACKGROUND AND OBJECTIVE: Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them. MATERIAL AND METHODS: Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020. RESULTS: A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas. CONCLUSIONS: ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

Venous thromboembolism incidence in cancer patients with germline BRCA mutations.

BACKGROUND: Germline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown. MATERIALS AND METHODS: We performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Marañón, Spain, from 2010 to 2019. RESULTS: One-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients. CONCLUSIONS: The VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.

Use of Chelex-100 for the molecular diagnosis of five animal pathogens / Uso de Chelex-100 para el diagnóstico molecular de cinco patógenos de animales

Abstract Molecular tools have improved conventional veterinary diagnosis. Acid nucleic extraction is a key step for downstream applications. This work aimed to compare the DNA extraction method Chelex-100 resin (M1) with Whatman® cards (M2), phenol-chloroform (M3), or commercial kits (M4), and to determine the most sensitive and inexpensive one for its diagnosis of animal pathogens that, despite their economic or zoonotic relevance, receive little attention. DNA was isolated from urine, organs, semen, blood and intestinal mucous, from the bacteria Leptospira interrogans serovar Pomona Pomona (by M1 and M2), Brucella melitensis (by M1, M3 and M4), and Salmonella ser. Abortusequi (by M1 and M4), and the parasites Leishmania spp. (by M1, M3 and M4), and Eimeria spp. (by M1 and M3), respectively. The sensitivity of each method was assayed by Polymerase Chain Reaction (PCR). The M1 showed similar sensitivity for Salmonella ser. Abortusequi, Leishmania spp., and Eimeria spp., being better for L. interrogans serovar Pomona Pomona and slightly lower for B. melitensis. For the first time, a simple and economic method was successfully employed for extracting DNA from these animal pathogens, especially important in low-resource settings, contributing to the diagnosis of leptospirosis, brucellosis, leishmaniasis, and coccidiosis; as well as to the molecular epidemiology of salmonellosis in stallion from semen samples.

Resumen Las técnicas moleculares han contribuido a mejorar el diagnóstico veterinario tradicional y la extracción de ácidos nucleicos es determinante. El objetivo de este trabajo fue comparar el método de extracción de ADN Chelex-100 (M1) con papel Whatman (M2), fenol-cloroformo (M3) o kits comerciales (M4), y determinar un método sensible y de bajo costo para el diagnóstico de patógenos de animales económica o zoonóticamente relevantes y que reciben poca atención. A partir de orina, órganos, semen, sangre y mucosa intestinal se extrajo el ADN de las bacterias Leptospira interrogans serovar Pomona Pomona (con M1 y M2), Brucella melitensis (con M1, M3 y M4), Salmonella ser. Abortusequi (M1 y M4), y de los parásitos Leishmania spp. (M1, M3 y M4) y Eimeria spp. (M1 y M3), respectivamente. La sensibilidad de los protocolos fue analizada por PCR. El método M1 demostró una sensibilidad similar para S. Abortusequi, Leishmania spp. y Eimeria spp., siendo mejor para L. interrogans y levemente menor para B. melitensis. Por primera vez se usó exitosamente en estos patógenos veterinarios un método simple y económico para extraer ADN, especialmente importante en laboratorios de bajos recursos económicos, contribuyendo al diagnóstico de leptospirosis, brucelosis, leishmaniasis y coccidiosis, así como también a la epidemiología molecular de salmonelosis en muestras de semen de caballos.

Advances in research on the impacts of anti-submarine sonar on beaked whales.

Mass stranding events (MSEs) of beaked whales (BWs) were extremely rare prior to the 1960s but increased markedly after the development of naval mid-frequency active sonar (MFAS). The temporal and spatial associations between atypical BW MSEs and naval exercises were first observed in the Canary Islands, Spain, in the mid-1980s. Further research on BWs stranded in association with naval exercises demonstrated pathological findings consistent with decompression sickness (DCS). A 2004 ban on MFASs around the Canary Islands successfully prevented additional BW MSEs in the region, but atypical MSEs have continued in other places of the world, especially in the Mediterranean Sea, with examined individuals showing DCS. A workshop held in Fuerteventura, Canary Islands, in September 2017 reviewed current knowledge on BW atypical MSEs associated with MFAS. Our review suggests that the effects of MFAS on BWs vary among individuals or populations, and predisposing factors may contribute to individual outcomes. Spatial management specific to BW habitat, such as the MFAS ban in the Canary Islands, has proven to be an effective mitigation tool and mitigation measures should be established in other areas taking into consideration known population-level information.

Reducción del Riesgo en Equipos Biomédicos y en Instalaciones Eléctricas de Entornos Clínicos / Risk Reduction in Electrical Networks and Safety of Biomedical Equipment in Clinical Settings

Resumen Se analizan 112 auditorías de instalaciones eléctricas y seguridad de equipos biomédicos en 78 Institutos de Medicina Altamente Especializada (IMAE) del Uruguay, realizadas a lo largo de 14 años, clasificando el nivel de riesgo y de cumplimiento de normas desde el punto de vista de Ingeniería Clínica. Cada visita incluye una encuesta al personal encargado de mantener y gestionar la infraestructura eléctrica y el equipamiento biomédico, que abarca el estado de mantenimiento, el control y la documentación de las instalaciones eléctricas y del equipamiento biomédico. Se evalúa el riesgo con un puntaje de 0 a 4. En 2004-2007 el 74% de los IMAE tenía irregularidades en la instalación eléctrica, gestión de equipamiento, control de calidad o documentación. Además, un 15% de los que tenían problemas, tenía en particular equipamiento indicado como "equipo peligroso". En los períodos siguientes esta proporción baja paulatinamente hasta 0% en 2016-2017. No obstante, continúa existiendo un déficit en la gestión del equipamiento y en la documentación formal. El aporte de la Universidad en el seguimiento técnico de los IMAE se ha materializado en una mejora en materia de seguridad.

Abstract 112 field inspections to 78 high technology medical centers (IMAE is the Spanish acronym) over 14 years are analyzed. All visits were evaluated as to Clinical Engineering good practices and were assigned a risk level. All audits included a questionaire to maintenance management personnel on electrical network operation as well as on biomedical equipment follow-up and documentation from acquisition to disposal. Risk is assigned a level 0 to 4 at each visit. In 2004-2007, 74% of IMAEs had safety problems in one or more of electrical network, maintenance management or documentation, and 15% of the IMAEs with safety problems had one piece of equipment described as simply "dangerous". Electrical safety problems were eventually reduced to 0% in 2016-2017, probably as a consequence of regular audit and counseling by this University Clinical Engineering Program.

Recombinant protein purification in baculovirus-infected Rachiplusia nu larvae: An approach towards a rational design of downstream processing strategies based on chromatographic behavior of proteins.

Expression of recombinant proteins with baculovirus-infected insect larvae is a scarcely investigated alternative in comparison to that in insect cell lines, a system with growing popularity in the field of biotechnology. The aim of this study was to investigate the chromatographic behavior and physicochemical properties of the proteome of Rachiplusia nu larvae infected with recombinant Autographa californica multiple nucleopolyhedrosis virus (AcMNPV), in order to design rational purification strategies for the expression of heterologous proteins in this very complex and little-known system, based on the differential absorption between target recombinant proteins and the system's contaminating ones. Two-dimensional (2D) gel electrophoresis showed differences in the protein patterns of infected and non-infected larvae. Hydrophobic interaction matrices adsorbed the bulk of larval proteins, thus suggesting that such matrices are inappropriate for this system. Only 0.03% and 2.9% of the total soluble protein from the infected larval extract was adsorbed to CM-Sepharose and SP-Sepharose matrices, respectively. Immobilized metal ion affinity chromatography represented a solid alternative because it bound only 1.4% of the total protein, but would increase the cost of the purification process. We concluded that cation-exchange chromatography is the best choice for easy purification of high-isoelectric-point proteins and proteins with arginine tags, since very few contaminating proteins co-eluted with our target protein.

Atypical presentation of transthyretin amyloidosis in a non-endemic area. / Presentación atípica de amiloidosis por transtiretina en un área no endémica.

BACKGROUND AND OBJECTIVE: There are 2 types of amyloidosis caused by transthyretin deposits: the wild type (wt-ATTR) and the mutant type (m-ATTR), transmitted by autosomal dominant inheritance with variable penetrance, manifesting with neurological and/or cardiac symptoms. We report on 3 families affected by m-ATTR diagnosed in a nonendemic area. MATERIAL AND METHODS: We studied 63 patients with a high suspicion of ATTR. The diagnosis was subsequently performed by magnification through polymerase chain reaction of DNA. For the positive cases, we studied the first-degree relatives. RESULTS: We detected 7 positive cases of m-ATTR, distributed among 3 families (Glu74Gln, Val142Ile in heterozygosity and Val142Ile in homozygosity), and 3 cases of nonpathogenic variants. CONCLUSIONS: Hereditary ATTR is a rare disease but is present in nonendemic areas and should therefore be considered in the differential diagnosis of patients with polyneuropathy and/or heart failure with preserved ejection fraction.

Deadly acute Decompression Sickness in Risso's dolphins.

Diving air-breathing vertebrates have long been considered protected against decompression sickness (DCS) through anatomical, physiological, and behavioural adaptations. However, an acute systemic gas and fat embolic syndrome similar to DCS in human divers was described in beaked whales that stranded in temporal and spatial association with military exercises involving high-powered sonar. More recently, DCS has been diagnosed in bycaught sea turtles. Both cases were linked to human activities. Two Risso's dolphin (Grampus griseus) out of 493 necropsied cetaceans stranded in the Canary Islands in a 16-year period (2000-2015), had a severe acute decompression sickness supported by pathological findings and gas analysis. Deadly systemic, inflammatory, infectious, or neoplastic diseases, ship collision, military sonar, fisheries interaction or other type of lethal inducing associated trauma were ruled out. Struggling with a squid during hunting is discussed as the most likely cause of DCS.

Methodology for the assessment of brucellosis management practices and its vaccination campaign: example in two Argentine districts.

BACKGROUND: In Argentina, vaccination with Brucella abortus Strain 19 vaccine is mandatory. The objective of the study was to develop and test a method for evaluating, in an innovative way, some farmers' and veterinarians' management practices in relation to brucellosis and to assess the vaccination campaign and coverage. The work took place in Brandsen and Navarro districts. Four questionnaires were designed (for officials from Local Sanitary Entities, vaccinators, vet practitioners and farmers). Responses were coded as "ideal" (0) and "not ideal" (1). To assess the relative weight of each question ("item"), experts ranked the items according to their impact on management practices and vaccination. A weighted score was then calculated. A higher weighted score was assigned to the worse practices. Farmers obtaining a global weighted score above the third quartile were classified as "inappropriately managed farms", to be compared per type of production system and district. To assess the immunization coverage, female calves were sampled 30 to 50 days post vaccination; they were expected to react positively to serological diagnostic tests (DT+). RESULTS: There were significantly more inappropriately managed farms and higher global scores among beef farmers and in Brandsen. Eighty three percent (83%) of female calves were DT+, significantly under the ideal immunization coverage (95%). Only 48% of farms were considered well vaccinated. DT+ results were positively associated with the Brandsen district (OR = 25.94 [4.60-1146.21] and with the farms having more than 200 cow heads ((OR = 78.34 [4.09-1500.00]). On the contrary, DT+ were less associated with vaccinators being veterinary practitioners (OR = 0.07 [0.006-0.78]). Farmers are well advised by their veterinary practitioners but they should improve some management practices. CONCLUSIONS: The vaccination campaign is globally well implemented, but the immunization coverage and some vaccinators' practices should be improved. This study leads to a better understanding of the most common used management and control practices regarding brucellosis, which affect its epidemiology. Any vaccination campaign should be periodically assessed to highlight possible fails. The described methodology can be extrapolated to other countries and different contexts.

Predictors of Tumor Response to Cetuximab and Panitumumab in 116 Patients and a Review of Approaches to Managing Skin Toxicity.

INTRODUCTION AND OBJECTIVES: Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) in the treatment of metastatic colorectal cancer. Most patients develop a papulopustular rash, which may predict tumor response. We studied whether the other adverse cutaneous effects associated with these monoclonal antibodies are also clinical predictors of response. We also reviewed publications describing approaches to treating the papulopustular rash since no evidence-based guidelines have yet been published. MATERIAL AND METHODS: We performed a retrospective study of 116 patients with metastatic colorectal cancer receiving anti-EGRF therapy with cetuximab or panitumumab at Hospital Universitario Donostia. RESULTS: In total, 81.9% of the patients developed a papulopustular rash. Patients who received the most cycles of treatment with the EGFR inhibitor were at the highest risk of developing the rash, and these patients also had the most severe rash reactions (P=.03). All of the patients who exhibited a complete tumor response had the rash, and the incidence of rash was lower in patients with poor tumor response (P=.03). We also observed an association between tumor response and xerosis (53.4% of the patients who developed xerosis also exhibited tumor response, P=.002). The papulopustular rash was managed according to an algorithm developed by our department. CONCLUSIONS: Severe papulopustular rash and xerosis may be clinical predictors of good response to anti-EGFR therapy. Patients who develop a papulopustular rash should be treated promptly because suboptimal treatment of this and other adverse effects can lead to delays in taking the prescribed anti-EGFR dose or to interruption of therapy.

The association between nut consumption and the risk of total and ischemic stroke in a German cohort study.

BACKGROUND/OBJECTIVES: Nuts have beneficial effects on coronary heart disease and many cardiovascular risk factors. However, their effect on stroke is less established, and no studies on the topic are available in Northern and Central European populations. Therefore, we aimed at investigating the association between nut consumption and the risk of stroke in a German population. SUBJECTS/METHODS: We used data from a prospective cohort of 26,285 participants of the European Prospective Investigation into the Cancer and Nutrition Potsdam Study. During a median follow-up time of 8.3 years (interquartile range: 7.5-9.2), 288 incident cases of stroke occurred. Nut consumption (standard portion size of 50 g) was assessed at baseline with a semiquantitative food-frequency questionnaire. RESULTS: The median nut intake was 0.82 g per day, interquartile range: 0.41-4.11. In the multivariable model, an increased risk of stroke was observed among participants who never consumed nuts (hazard ratio (HR): 1.56, 95% confidence interval: 1.17-2.08), compared with those consuming <½ portion/week. However, there was no evidence of a dose-response relationship between nut consumption and stroke. Compared with those who consumed <½ portion/week, the multivariable HR for total stroke was 1.06 (0.75-1.52) among those who consumed ½ to 1 portion/week and 1.37 (0.92-2.05) for those who consumed >1 portion/week. Similar nonsignificant associations were observed in stratified analysis for gender, or for fatal and nonfatal stroke. CONCLUSIONS: We could not observe an association between nut consumption and the risk of developing stroke (fatal/nonfatal) in a population with low habitual nut consumption.

Manejo del cólico renal en urgencias de un hospital de tercer nivel / Nephritic colic management in an emergency room of a referral hospital

Fundamento. El objetivo del presente trabajo es conocerlas características epidemiológicas, el manejo diagnóstico yterapéutico, su seguimiento y la incidencia de diagnósticosalternativos en una muestra de pacientes diagnosticados decólico renal en el Servicio de Urgencias de un Hospital detercer nivel.Material y métodos. Estudio descriptivo retrospectivo de182 pacientes seleccionados aleatoriamente que consultanpor clínica compatible con cólico renal en un hospital detercer nivel, valorando su manejo inicial, seguimiento al altay diagnósticos alternativos.Resultados. El 55,4% fueron varones, la edad media fue de47,7 años y el 40% de los casos se produjeron en primavera.En todos los pacientes se realizó analítica urinaria (62,7%tira reactiva y 72% sedimento) apareciendo alteraciones enmás del 70%. La función renal se deterioró en el 26,4 % delos casos, siempre de forma transitoria. La prueba de imagenrealizada con más frecuencia fue la radiografía de abdomen(81,9%) seguida de la ecografía (25,8%). El tratamiento incluyófluidoterapia en el 31,3% y el analgésico más usado fue elmetamizol (61%) seguido del ketorolaco (44,5%). El 46,2% delos pacientes necesitó más de un analgésico. Un total de 24pacientes precisaron ingreso hospitalario y 5 de ellos cirugíaurgente. El 24,1% presentó recaídas en los seis meses posteriores.El 41,6% fue remitido al Servicio de Urología al alta. El18,1% presentaron diagnósticos alternativos, siendo la pielonefritisaguda el más frecuente de ellos (55%).Conclusiones. Hemos detectado una importante variaciónen el manejo diagnóstico y terapéutico de estos pacientes.El uso de guías clínicas debe permitirnos unificar el manejodel paciente con cólico renal tanto en urgencias como posteriormente.El alto porcentaje de diagnósticos alternativosnos obliga a descartar sistemáticamente patologías másgraves(AU)

Background. To evaluate the diagnostic and therapeuticmanagement of patients with nephritic colic in a referralhospital, their monitoring and the incidence of alternativediagnoses.Methods. This is a retrospective review of 182 randomly selectedpatients who presented a clinical diagnosis compatiblewith nephritic colic in a referral hospital. In these casesinitial treatment, monitoring and alternative diagnoses havebeen evaluated.Results. Fifty-five point four percent of the patients weremale, the mean age was 47.7 years and 40% of the cases werein spring. Urinalysis was carried out in every patient (62.7%dipstick and 72% urinary sediment); they were pathologicalin over 70%. In 26.4% of cases renal function deteriorated,always transiently. Abdominal radiography (81.9%) was themost frequently diagnostic test performed, followed by ultrasound(25.8%). Treatment included a serum therapy in 31.3%;metamizol (61%) was the most commonly used analgesic followedby ketorolac (44.5%). More than one non-steroidal anti-inflammatory was used by 46.2%. Hospital admission wasrequired by 24 patients, and 5 of them needed emergencysurgery. Twenty-four point one percent of patients had relapsesduring the next six months. Forty-one point six percentwere referred to urology discharge on from the emergencyroom. Eighteen point one percent of patients had alternativediagnoses; acute pyelonephritis was the most frequent ofthese (55%).Conclusions. In our work we found a significant variationin the diagnostic and therapeutic management of these patients.The use of clinical guidelines could help us to unifythe management of patients with nephritic colic, both in theemergency room and on discharge. Due to the high prevalenceof alternative diagnoses, we have to systematicallyexclude more serious diseases(AU)