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1.
J Fr Ophtalmol ; 47(4): 104138, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484481

RESUMO

PURPOSE: To present the clinical, genetic, and histopathological features of the ninth family affected by congenital stromal corneal dystrophy (CSCD) to date. METHODS: Twelve cases of a Spanish family affected by CSCD were analyzed regarding history, visual acuity (VA, decimal scale), an ophthalmologic exam and specular microscopy. Five eyes were treated by deep anterior lamellar keratoplasty (DALK), and thirteen eyes by penetrating keratoplasty (PK). In the two last generations, a genetic study was performed. RESULTS: Most of the patients affected were born with opaque corneas except for three, whose corneas were clear at birth. Biomicroscopy showed a whitish diffuse stromal opacity with an unaltered epithelium, causing poor VA (from hand motions to 0.4). Patients treated with PK presented mean postoperative VA of 0.19±0.20 over a follow-up time of 235.3±101.4months with 38% recurrences. Patients who underwent DALK experienced VA improvement to 0.17±0.11 over a follow-up time of 10.8±2.6months without signs of recurrence. In the latter, the big bubble technique was not achieved, so a manual technique was performed. The genetic study showed heterozygosis for a 1-bp deletion at nucleotide 962 in exon 8 of the decorin gene. CONCLUSIONS: CSCD is a rare entity, which should be treated by DALK whenever possible, obtaining better results than PK. Close monitoring of children of affected individuals is important, because CSCD can progress during the early years of life.


Assuntos
Distrofias Hereditárias da Córnea , Transplante de Córnea , Ceratocone , Criança , Recém-Nascido , Humanos , Transplante de Córnea/métodos , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/patologia , Ceratoplastia Penetrante , Endotélio Corneano/patologia , Estudos Retrospectivos , Resultado do Tratamento , Ceratocone/cirurgia
2.
Heliyon ; 10(4): e26353, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404851

RESUMO

Biological and mechanical biological treatment plants combine mechanical and biological treatments to recover the greatest possible amount of materials from municipal solid waste (MSW) and biostabilize the organic fraction to be landfilled or applied in land. These plants handle a high percentage of the MSW generated in Europe. This work presents an exhaustive analysis of the existing plants in Spain which evaluates their typology as well as their performance. In Spain, 137 plants, which receive 13 Mt/year of waste, provide the country with total coverage. Twenty-two types of plants have been identified and grouped into six categories. There are four categories that receive mixed MSW: 1) sorting plants; 2) recovery and composting plants; 3) biodrying and recovery plants; and 4) recovery, biomethanation and composting plants and two that receive separately collected biowaste: 5) composting plants, and 6) biomethanation and composting plants. In plants that receive mixed waste, around 5% of the total input is recovered as recyclable materials (662,182 t/year), of which 29% corresponds to plastics, 27% to metals, and 27% to paper and cardboard. In addition, biostabilized material and/or biogas, and rejects (45-77% of the input) are obtained. In the biowaste plants, high-quality compost (more than 105,000 t/year), a higher biogas yield (43.60 Nm3/t·year) and a lower proportion of rejects (around 29%) are obtained.

3.
Nat Commun ; 14(1): 4954, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587123

RESUMO

Submolecular charge distribution significantly affects the physical-chemical properties of molecules and their mutual interaction. One example is the presence of a π-electron-deficient cavity in halogen-substituted polyaromatic hydrocarbon compounds, the so-called π-holes, the existence of which was predicted theoretically, but the direct experimental observation is still missing. Here we present the resolution of the π-hole on a single molecule using the Kelvin probe force microscopy, which supports the theoretical prediction of its existence. In addition, experimental measurements supported by theoretical calculations show the importance of π-holes in the process of adsorption of molecules on solid-state surfaces. This study expands our understanding of the π-hole systems and, at the same time, opens up possibilities for studying the influence of submolecular charge distribution on the chemical properties of molecules and their mutual interaction.

4.
Anal Methods ; 15(16): 1969-1978, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37051732

RESUMO

A methodology based on the ultrasound-assisted extraction with ethanol and the dry film attenuated total reflectance infrared spectroscopy (DF-ATR-FTIR) measurement of extracts has been developed for a fast evaluation of non-conventional ("exotic") solid-sized cocaine samples. The method provides quantitative results in less than three minutes with a limit of detection in the solid sample of 1.6 µg g-1 of cocaine with a variation coefficient lower than 7%. Results found for seized samples of different natures were compared with those obtained by a reference gas chromatography method and the greenness of the whole proposed procedure was evaluated and compared using the analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness metric (AGREE). The green evaluation of the proposed methodology provided green scores by considering different evaluation criteria.


Assuntos
Cocaína , Cocaína/análise , Cocaína/química , Espectrofotometria Infravermelho , Cromatografia Gasosa
5.
Rev Med Chil ; 150(3): 316-323, 2022 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-36156716

RESUMO

BACKGROUND: In a decade, we faced two pandemic viruses, influenza A H1N1pdm09 and SARS CoV-2, whose most serious manifestation is pneumonia. AIM: To compare the clinical, epidemiological and management aspects of pneumonias caused by each pandemic virus in adults requiring hospitalization. MATERIAL AND METHODS: Comparative, observational study carried out at a regional Chilean hospital, including 75 patients with influenza A H1N1pdm09 prospectively studied in 2009 and 142 patients with SARS-CoV-2 studied in 2020. RESULTS: Patients with SARS-CoV-2 pneumonia were older (56 and 39.7 years respectively, p < 0.01) and had significantly more comorbidities. Cough, fever and myalgias were more frequent in influenza. Dyspnea was more frequent in COVID-19. Patients with COVID-19 had more extensive lung involvement and a longer hospitalization (13.6 and 8.6 days respectively, p = 0.01). There was no difference on ICU admission requirements and mortality attributable to pneumonia. Patients with influenza had greater APACHE scores and a higher frequency of a PaO2/FiO2 ratio ≤ 200. During COVID-19pandemic chest sean replaced x-ray examination. Also high-flow nasal cannulas and awake prone position ventilation were added as treatments. CONCLUSIONS: COVID-19 patients were older, had fewer classic flu symptoms but more dyspnea and longer hospitalization periods than patients with influenza.


Assuntos
COVID-19 , Influenza Humana , Pneumonia Viral , Adulto , COVID-19/epidemiologia , Dispneia , Hospitalização , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , SARS-CoV-2
6.
Rev Med Chil ; 150(4): 465-472, 2022 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-36155756

RESUMO

BACKGROUND: The COVID-19 pandemic posed a great strain in health services. AIM: To describe the epidemiological and clinical features of patients with SARS-CoV-2 admitted to a regional hospital in southern Chile between April and August 2020. MATERIAL AND METHODS: Clinical records of all hospitalized patients with RT-PCR (+) for SARS-CoV-2 were retrospectively analyzed. RESULTS: During the study period 226 patients aged 55 ± 18 years (55% men) were admitted. The main comorbidities were high blood pressure in 45%, diabetes in 31% and obesity in 21%. The main symptoms were dyspnea in 70%, cough in 69%, fever in 62% and myalgia in 47%. Pneumonia was the main cause of admission in 66%. Images on admission were compatible with pneumonia in 81%, and with a typical COVID-19 pattern in 84%. In 76% there was five-lobe involvement. Eighty-seven cases (39%) were admitted to critical care, with an APACHE score of 10.9 ± 7.1. Invasive mechanical ventilation was used in 16%, 30% required prone position and 13%, a high-flow nasal cannula. The mean stay in critical care was 13.3 days. The mean duration of invasive mechanical ventilation was 14.1 days. Antimicrobials were used in 55% and dexamethasone in 36%. Twenty-two (9.7%) patients aged 71.7 ± 14 died. A Charlson comorbidity index > 3, heart failure and connection to invasive mechanical ventilation were independent risk factors for death. An age > 65 years alone and other comorbidities were not risk factors. CONCLUSIONS: Viral pneumonia is the main cause of hospitalization for COVID-19, usually extensive and bilateral. The greater severity and poor prognosis of these patients are mainly related to comorbidities.


Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , Chile/epidemiologia , Dexametasona , Feminino , Hospitalização , Hospitais , Humanos , Masculino , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2
7.
Int. j. psychol. psychol. ther. (Ed. impr.) ; 22(2): 177-184, jun. 2022. tab
Artigo em Inglês | IBECS | ID: ibc-207432

RESUMO

COVID-19 seriously affected people’s mental health. Possibly symptoms of anxiety, depression and insomnia occur with most frequency in various sectors of the population, especially in mothers. The objective of this research was to evaluate levels of depression, anxiety and insomnia in Mexican mothers who had COVID-19, who care for or cared for patients with COVID-19, or in neither of these two conditions. A sample of 540 Mexican mothers was gathered, a questionnaire was applied to obtain data on sociodemographic variables, as well as instruments to measure depression, anxiety and insomnia. The 70% of the participants had insomnia, 77% had depressive symptoms, while 80.2% showed anxiety. Working mothers presented more severe symptoms of insomnia than housewives. Caring for a COVID-19 patient was significantly associated with the psychological variables evaluated. Mexican mothers who care or cared for COVID-19 patients have high rates of depression, anxiety, and insomnia (AU)


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Infecções por Coronavirus/psicologia , Pneumonia Viral/psicologia , Pandemias , Mães/psicologia , Depressão/psicologia , Ansiedade/psicologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Cuidadores/psicologia , Inquéritos e Questionários , México
8.
Rev. méd. Chile ; 150(4): 465-472, abr. 2022. tab
Artigo em Espanhol | LILACS | ID: biblio-1409832

RESUMO

BACKGROUND: The COVID-19 pandemic posed a great strain in health services. AIM: To describe the epidemiological and clinical features of patients with SARS-CoV-2 admitted to a regional hospital in southern Chile between April and August 2020. MATERIAL AND METHODS: Clinical records of all hospitalized patients with RT-PCR (+) for SARS-CoV-2 were retrospectively analyzed. RESULTS: During the study period 226 patients aged 55 ± 18 years (55% men) were admitted. The main comorbidities were high blood pressure in 45%, diabetes in 31% and obesity in 21%. The main symptoms were dyspnea in 70%, cough in 69%, fever in 62% and myalgia in 47%. Pneumonia was the main cause of admission in 66%. Images on admission were compatible with pneumonia in 81%, and with a typical COVID-19 pattern in 84%. In 76% there was five-lobe involvement. Eighty-seven cases (39%) were admitted to critical care, with an APACHE score of 10.9 ± 7.1. Invasive mechanical ventilation was used in 16%, 30% required prone position and 13%, a high-flow nasal cannula. The mean stay in critical care was 13.3 days. The mean duration of invasive mechanical ventilation was 14.1 days. Antimicrobials were used in 55% and dexamethasone in 36%. Twenty-two (9.7%) patients aged 71.7 ± 14 died. A Charlson comorbidity index > 3, heart failure and connection to invasive mechanical ventilation were independent risk factors for death. An age > 65 years alone and other comorbidities were not risk factors. CONCLUSIONS: Viral pneumonia is the main cause of hospitalization for COVID-19, usually extensive and bilateral. The greater severity and poor prognosis of these patients are mainly related to comorbidities.


Assuntos
Humanos , Masculino , Feminino , Pandemias , COVID-19/epidemiologia , Respiração Artificial , Dexametasona , Chile/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Hospitalização , Hospitais
10.
Rev. méd. Chile ; 150(3): 316-323, mar. 2022. tab
Artigo em Espanhol | LILACS | ID: biblio-1409804

RESUMO

BACKGROUND: In a decade, we faced two pandemic viruses, influenza A H1N1pdm09 and SARS CoV-2, whose most serious manifestation is pneumonia. AIM: To compare the clinical, epidemiological and management aspects of pneumonias caused by each pandemic virus in adults requiring hospitalization. Material and Methods: Comparative, observational study carried out at a regional Chilean hospital, including 75 patients with influenza A H1N1pdm09 prospectively studied in 2009 and 142 patients with SARS-CoV-2 studied in 2020. RESULTS: Patients with SARS-CoV-2 pneumonia were older (56 and 39.7 years respectively, p < 0.01) and had significantly more comorbidities. Cough, fever and myalgias were more frequent in influenza. Dyspnea was more frequent in COVID-19. Patients with COVID-19 had more extensive lung involvement and a longer hospitalization (13.6 and 8.6 days respectively, p = 0.01). There was no difference on ICU admission requirements and mortality attributable to pneumonia. Patients with influenza had greater APACHE scores and a higher frequency of a PaO2/FiO2 ratio ≤ 200. During COVID-19pandemic chest sean replaced x-ray examination. Also high-flow nasal cannulas and awake prone position ventilation were added as treatments. Conclusions: COVID-19 patients were older, had fewer classic flu symptoms but more dyspnea and longer hospitalization periods than patients with influenza.


Assuntos
Humanos , Adulto , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/epidemiologia , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , COVID-19/epidemiologia , Dispneia , Pandemias , SARS-CoV-2 , Hospitalização
11.
Fisioterapia (Madr., Ed. impr.) ; 44(2): 71-79, mar.-abr. 2022. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-203746

RESUMO

La situación sanitaria generada por la aparición de la COVID-19 ha precipitado el uso de nuevas tecnologías y la adaptación de los servicios de rehabilitación de todo tipo. Objetivo: Describir la implementación de un sistema de telerehabilitación en pacientes con diferentes diagnósticos de discapacidad que viven en alta latitud sur, durante la pandemia de COVID-19. Métodos: Se implementó un sistema de terapias personalizadas guiadas mediante videoconferencia para pacientes con diferentes diagnósticos de discapacidad. Los pacientes se agruparon en tres grupos etarios (menores, adultos, adultos mayores) y seis tipos de diagnóstico clínico (afecciones originadas en el periodo perinatal, enfermedades del sistema circulatorio, enfermedades del sistema nervioso, enfermedades del sistema osteomuscular y del tejido conjuntivo, tratamientos mentales y del comportamiento y otro tipo de diagnósticos). Se evaluó el diagnóstico del paciente, el tipo de atención requerida, el número de sesiones y el nivel de satisfacción de cada usuario en función de la telerehabilitación que recibieron. Resultados: Participaron 101 pacientes con edad promedio de 31±26 años, siendo el 52,5% de estos del sexo masculino. Todos ellos logran manejar tecnologías mínimas requeridas para la atención por telerehabilitación. Existe un grado de asociación entre el diagnóstico del paciente y el grupo etario (p<0,05), así como también entre el diagnóstico y el tipo de atención requerida (p<0,05). Tras la implementación, los usuarios y usuarias evalúan positivamente la terapia a distancia. Conclusiones: La telerehabilitación puede ser implementada en pacientes con discapacidad en zonas de alta latitud sur, respetando las diferentes etapas del proceso, para asegurar una correcta ejecución.


The health situation after the emergence of COVID-19 has precipitated the use of new technologies and the adaptation of rehabilitation services of all kinds. Objective: To describe the implementation of a telerehabilitation system in patients with different diagnoses of disability living in the high southern latitude during the COVID-19 pandemic. Methods: A system of personalized therapies guided by videoconference was implemented for patients with varying diagnoses of disability. The patients were grouped into three age groups (Minors; Adults; Older Adults) and six types of clinical diagnosis (conditions originating in the perinatal period, diseases of the circulatory system, diseases of the nervous system, diseases of the musculoskeletal system, and connective tissue, mental and behavioural treatments and other diagnoses). The patient's diagnosis, the type of care required, the number of sessions, and the level of satisfaction of each user were evaluated based on the telerehabilitation they received. Results: 101 patients with an average age of 31±26 years participated, 52.5% were male. All of them managed to handle the minimum technologies required for telerehabilitation care. There is a degree of association between the patient's diagnosis and the age group (p<.05), as well as between the diagnosis and the type of care required (p<.05). After implementation, users positively evaluated distance therapy. Conclusions: Telerehabilitation can be implemented in patients with disabilities in areas of high southern latitude, respecting the different stages of the process, to ensure it is correctly delivered.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Telerreabilitação/métodos , Pessoas com Deficiência/reabilitação , Infecções por Coronavirus , Chile , Aconselhamento a Distância , Telerreabilitação/organização & administração , Telerreabilitação/estatística & dados numéricos , Epidemiologia Descritiva , Estudos Longitudinais , Estudos Retrospectivos
12.
Artigo em Inglês | MEDLINE | ID: mdl-34995899

RESUMO

BACKGROUND: Obesity is a worldwide public health problem characterized by fat tissue accumulation, favouring adipose tissue and metabolic alterations. Increasing energy expenditure (EE) through brown adipose tissue activation and white adipose tissue (WAT) browning has gained relevance as a therapeutic approach. Different bioactive compounds, such as n-3 polyunsaturated fatty acids (PUFA), have been shown to induce those thermogenic effects. This process is regulated by the gut microbiota as well. Nevertheless, obesity is characterized by gut microbiota dysbiosis, which can be restored by weight loss and n-3 PUFA intake, among other factors. Knowledge gap: However, the role of the gut microbiota on the n-3 PUFA effect in inducing thermogenesis in obesity has not been fully elucidated. OBJECTIVE: This review aims to elucidate the potential implications of this interrelation on WAT browning adiposw sittue (BAT), BAT activity, and EE regulation in obesity models.


Assuntos
Ácidos Graxos Ômega-3 , Microbioma Gastrointestinal , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Ácidos Graxos Ômega-3/metabolismo , Humanos , Obesidade/metabolismo , Termogênese
15.
Science ; 374(6569): 863-867, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34762455

RESUMO

An anisotropic charge distribution on individual atoms, such as σ-holes, may strongly affect the material and structural properties of systems. However, the spatial resolution of such anisotropic charge distributions on an atom represents a long-standing experimental challenge. In particular, the existence of the σ-hole on halogen atoms has been demonstrated only indirectly through the determination of the crystal structures of organic molecules containing halogens or with theoretical calculations, consequently calling for its direct experimental visualization. We show that Kelvin probe force microscopy with a properly functionalized probe can image the anisotropic charge of the σ-hole and the quadrupolar charge of a carbon monoxide molecule. This opens a new way to characterize biological and chemical systems in which anisotropic atomic charges play a decisive role.

18.
Med. intensiva (Madr., Ed. impr.) ; 44(8): 500-508, nov. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-198557

RESUMO

El traumatismo craneoencefálico grave (TCEg) continúa siendo prevalente en la población adulta joven. Lejos de descender, su incidencia se mantiene elevada. Uno de los pilares en los que se asienta su tratamiento es evitar, detectar y corregir complicaciones secundarias de origen sistémico que agravan la lesión primaria. Gran parte de este objetivo se logra manteniendo un microambiente fisiológico adecuado que permita la recuperación del tejido cerebral lesionado. Las medidas de cuidados generales son acciones inespecíficas destinadas a cumplir dicho objetivo. Las guías disponibles de manejo del TCEg no han incluido la mayoría de los tópicos motivo de este consenso. Para ello, hemos reunido un grupo de profesionales miembros del Consorcio latinoamericano de Injuria Cerebral (LABIC), involucrados en los diferentes aspectos del manejo agudo del TCEg (neurocirujanos, intensivistas, anestesiólogos, neurólogos, enfermeros, fisioterapeutas). Se efectuó una búsqueda bibliográfica en las bases de datos LILACS, PubMed, Embasse, Scopus, Cochrane Controlled Register of Trials y Web of Science de los tópicos seleccionados. Para establecer recomendaciones o sugerencias con su respectiva fortaleza o debilidad, fue aplicada la metodología Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Adicionalmente, ciertas recomendaciones (incluidas en material complementario) no fueron valoradas por GRADE, por ser las mismas un conjunto de acciones terapéuticas de cumplimento efectivo, en las que no fue posible aplicar dicha metodología. Fueron establecidas 32 recomendaciones; 16 fuertes y 16 débiles, con su respectivo nivel de evidencia. El presente consenso intenta homogeneizar y establecer medidas de cuidados generales básicas en esta población de individuos


Severe traumatic brain injury (sTBI) remains prevalent in the young adult population. Indeed, far from descending, the incidence of sTBI remains high. One of the key bases of treatment is to avoid, detect and correct secondary injuries of systemic origin, which aggravate the primary lesion. Much of this can be achieved by maintaining an adequate physiological microenvironment allowing recovery of the damaged brain tissue. General care measures are nonspecific actions designed to meet that objective. The available guidelines on the management of sTBI have not included the topics contemplated in this consensus. In this regard, a group of members of the Latin American Brain Injury Consortium (LABIC), involved in the different aspects of the acute management of sTBI (neurosurgeons, intensivists, anesthesiologists, neurologists, nurses and physiotherapists) were gathered. An exhaustive literature search was made of selected topics in the LILACS, PubMed, Embase, Scopus, Cochrane Controlled Register of Trials and Web of Science databases. To establish recommendations or suggestions with their respective strength or weakness, the GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was applied. Additionally, certain recommendations (included in complementary material) were not assessed by GRADE, because they constitute a set of therapeutic actions of effective compliance, in which it was not possible to apply the said methodology. Thirty-two recommendations were established, 16 strong and 16 weak, with their respective levels of evidence. This consensus attempts to standardize and establish basic general care measures in this particular patient population


Assuntos
Humanos , Conferências de Consenso como Assunto , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Cranianos Penetrantes/terapia , Neuroproteção/fisiologia , Traumatismos Craniocerebrais/fisiopatologia , Respiração Artificial/normas , Intubação/normas
20.
Med Intensiva (Engl Ed) ; 44(8): 500-508, 2020 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32376092

RESUMO

Severe traumatic brain injury (sTBI) remains prevalent in the young adult population. Indeed, far from descending, the incidence of sTBI remains high. One of the key bases of treatment is to avoid, detect and correct secondary injuries of systemic origin, which aggravate the primary lesion. Much of this can be achieved by maintaining an adequate physiological microenvironment allowing recovery of the damaged brain tissue. General care measures are nonspecific actions designed to meet that objective. The available guidelines on the management of sTBI have not included the topics contemplated in this consensus. In this regard, a group of members of the Latin American Brain Injury Consortium (LABIC), involved in the different aspects of the acute management of sTBI (neurosurgeons, intensivists, anesthesiologists, neurologists, nurses and physiotherapists) were gathered. An exhaustive literature search was made of selected topics in the LILACS, PubMed, Embase, Scopus, Cochrane Controlled Register of Trials and Web of Science databases. To establish recommendations or suggestions with their respective strength or weakness, the GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was applied. Additionally, certain recommendations (included in complementary material) were not assessed by GRADE, because they constitute a set of therapeutic actions of effective compliance, in which it was not possible to apply the said methodology. Thirty-two recommendations were established, 16 strong and 16 weak, with their respective levels of evidence. This consensus attempts to standardize and establish basic general care measures in this particular patient population.

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