Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.
Optic Atrophy, Hereditary, Leber , Ubiquinone/analogs & derivatives , Humans , Optic Atrophy, Hereditary, Leber/drug therapy , Optic Atrophy, Hereditary, Leber/genetics , Optic Atrophy, Hereditary, Leber/diagnosis , Antioxidants/therapeutic use , Ubiquinone/therapeutic use , Ubiquinone/genetics , Mutation
PURPOSE OF REVIEW: The present review will highlight recent reports supporting the relevance of extracellular vesicles to the musculoskeletal system in health and disease. RECENT FINDINGS: Preserving the health of the musculoskeletal system is important to maintain a good quality of life, and the bone-muscle crosstalk is crucial in this regard. This latter is largely mediated by extracellular vesicles released by the different cell populations residing in muscle and bone, which deliver cargoes, microRNAs, and proteins being the most relevant ones, to target cells. Extracellular vesicles could be exploited as therapeutic tools, in view of their resistance to destruction in the biological fluid and of the possibility to be functionalized according to the need. Extracellular vesicles are recognized as crucial players in the bone-muscle cross-talk. Additional studies however are required to refine their use as biomarkers of early alterations of the musculoskeletal system, and as potential therapeutic tools.
Exosomes , Extracellular Vesicles , MicroRNAs , Humans , Extracellular Vesicles/metabolism , Exosomes/metabolism , Muscle, Skeletal/metabolism , Musculoskeletal Diseases/metabolism , Bone and Bones/metabolism , Biomarkers/metabolism , Musculoskeletal System/metabolism
PURPOSE: The role of the choroid in Leber hereditary optic neuropathy (LHON) remains unclear. The literature is scarce, with conflicting results and lacks axial length measurements. Therefore, we aimed to analyse the choriocapillaris (CC) vessel density (VD) and choroidal thickness (ChT) in all stages of LHON using swept source (SS) technology and considering the possible influence of axial length on choroidal parameters. METHODS: This was a prospective cross-sectional observational study. A total of 119 eyes of 60 patients with molecularly confirmed LHON across all stages and 120 eyes of 60 control participants were included. We obtained the CC VD using optical coherence tomography angiography maps centred on the fovea. ChT was measured from the Bruch's membrane to the choroid-sclera interface in the macular and peripapillary regions. RESULTS: The CC VD was not significantly affected in any sector or average, except for a slight change in the superior region of chronic eyes (52.08 ± 1.62% vs. 53.50 ± 2.29%, p = 0.002). ChT demonstrated a trend towards decreased values in asymptomatic eyes and increased values in the symptomatic stages that failed to reach statistical significance in sectors corresponding to the papillomacular bundle except for the macular nasal inner sector of chronic eyes (281.10 ± 67.12 µm vs. 252.08 ± 70.55 µm, p = 0.045). No significant correlations were observed between visual acuity and CC VD or ChT. CONCLUSION: The CC VD remained stable across the LHON stages. Choroidal vasculature does not appear to play a role in LHON pathophysiology. Further research is needed on ChT as a potential biomarker of LHON.
BACKGROUND: Small non-coding (snc)RNAs, including microRNAs and P-element induced wimpy testis (PIWI)-interacting-RNAs (piRNAs), crucially regulate gene expression in both physiological and pathological conditions. In particular, some muscle-specific microRNAs (myomiRs) have been involved in the pathogenesis of cancer-induced muscle wasting. The aims of the present study were (i) to profile sncRNAs in both skeletal muscle and plasma of gastrointestinal cancer patients and (ii) to investigate the association among differentially expressed sncRNAs and the level of muscularity at body composition analysis. METHODS: Surgical patients with gastrointestinal cancer or benign disease were recruited. Blood samples and muscle biopsies (rectus abdominis) were collected during surgery. Low muscularity patients were those at the lowest tertile of skeletal muscle index (SMI; CT-scan), whereas moderate/high muscularity patients were in the middle and highest SMI tertiles. SncRNAs in the muscle were assessed by RNAseq, circulating microRNAs were evaluated by qPCR. RESULTS: Cancer patients (n = 25; 13 females, 52%) showed a mean age of 71.6 ± 11.2 years, a median body weight loss of 4.2% and a mean BMI of 27.0 ± 3.2 kg/m2 . Control group (n = 15; 9 females, 60%) showed a mean age 58.1 ± 13.9 years and a mean BMI of 28.0 ± 4.3 kg/m2 . In cancer patients, the median L3-SMI (cm2 /m2 ) was 42.52 (34.42; 49.07). Males showed a median L3-SMI of 46.08 (41.17-51.79) and females a median L3-SMI of 40.77 (33.73-42.87). Moderate-high and low muscularity groups included 17 and 8 patients, respectively. As for circulating microRNAs, miR-21-5p and miR-133a-3p were up-regulated in patients compared with controls, whereas miR-15b-5p resulted down-regulated in the same comparison (about 30% of control values). Sample clustering by muscularity and sex revealed increased miR-133a-3p and miR-206 only in moderate-high muscularity males. SncRNA profiling in the muscle identified 373 microRNAs and 190 piRNAs (72.5% and 18.7% of raw reads, respectively). As for microRNAs, 10 were up-regulated, and 56 were down-regulated in cancer patients versus controls. Among the 24 dysregulated piRNAs, the majority were down-regulated, including the top two most expressed piRNAs in the muscle (piR-12790 and piR-2106). Network analysis on validated mRNA targets of down-regulated microRNAs revealed miR-15b-5p, miR-106a-5p and miR-106b-5p as main interactors of genes related to ubiquitin ligase/transferase activities. CONCLUSIONS: These results show dysregulation of both muscle microRNAs and piRNAs in cancer patients compared with controls, the former following a sex-specific pattern. Changes in circulating microRNAs are associated with the degree of muscularity rather than body weight loss.
Circulating MicroRNA , Gastrointestinal Neoplasms , MicroRNAs , RNA, Small Untranslated , Male , Female , Humans , Middle Aged , Aged , Aged, 80 and over , Adult , RNA, Small Untranslated/genetics , Piwi-Interacting RNA , Gene Expression Profiling , MicroRNAs/metabolism , Weight Loss
BACKGROUND: Cervical cytology is essential for the early detection of cervical cancer. However, in Colombia, only 50% of women with subsidized health insurance were screened in 2019, compared to 100% of women with contributory insurance. This disparity highlights significant barriers that must be addressed. This study aimed to identify the factors that contribute to or hinder adherence to cervical cytology screening among low-income women with subsidized health insurance in a public primary care network in Cali, Colombia, from 2014 to 2018. METHODS: In a qualitative case study, the experience of women and health care and administrative personnel was recovered. Forty-seven women participated in seven focus group discussions. Five other women using the program participated in in-depth interviews. Finally, we interviewed eight people from the healthcare area and the health services administration. The qualitative data collected underwent content analysis, guided by the theoretical framework of Social Determinants of Health. Within this framework, five interconnected dimensions that influence adherence were incorporated. RESULTS: Adherence is a multifactorial phenomenon, and in relation to attendance at cervical cytology, the analysis delved into the mechanisms that affect it in a low-income context. Barriers to adherence were identified across multiple dimensions, including social and economic factors, health conditions, and patient-related factors, among both adherent and non-adherent women. Among adherent women, barriers and facilitators related to the healthcare team and system, as well as patient-related factors, were identified. CONCLUSIONS: The findings of this research can be useful in developing personalized interventions and strategies to improve adherence and screening outcomes in low-income settings. It is necessary to increase the resources of health insurance entities to establish effective communication channels with women who attend the cervical cancer prevention program.
Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Colombia , Poverty , Vaginal Smears , Delivery of Health Care , Early Detection of Cancer
INTRODUCTION: Cachexia is a complex multi-factorial syndrome characterized by anorexia, inflammation, body, and skeletal muscle wasting. Early diagnosis and intervention via a multimodal approach combining nutritional counseling, exercise, and pharmacological agents is advisable. However, no effective treatment options are currently available in the clinical setting. AREAS COVERED: The present work is a review of emerging treatment options for cancer cachexia, including mainly, but not only, pharmacological approaches. The main interest is on drugs currently investigated in clinical trials; however, promising pre-clinical options are presented as well. Data were collected using PubMed and ClinicalTrials.gov databases, including studies of the last 20 years and active clinical trials. EXPERT OPINION: The lack of effective therapeutic approaches against cachexia results from several issues, among which a reduced number of studies focused on new drugs. Furthermore, the translation of pre-clinical results in the clinical practice is a hard mission, and it must be considered whether drugs target cachexia as a consequence of acting directly on the tumor. Indeed, dissecting antineoplastics from direct anti-cachexia effects is needed to elucidate the mechanisms of action of specific drugs. This is necessary for their inclusion into multimodal approaches, which nowadays are considered the best way to tackle cachexia.
Neoplasms , Humans , Neoplasms/complications , Cachexia/drug therapy , Cachexia/etiology , Exercise , Counseling
OBJETIVO: Estimar la prevalencia de la ideación suicida (IS) y su asociación con los determinantes sociales (DS) en la pobla-ción mexicana durante la pandemia de Covid-19. Material y métodos. Datos de la encuesta de Atención Psicológica a Distancia para la Salud Mental debido a la Contingencia por Covid-19 obtenidos durante 2020. La muestra fue de 79 665. Se realizaron modelos de regresión logística obteniendo razones de momios (RM) con intervalos de confianza del 95% (IC95%). RESULTADOS: La prevalencia de IS fue de 17.1% (mujeres:18.8% y hombres: 14.4%). Principales DS asociados fueron: ser mujer (RM=1.11; IC95% 1.06,1.13), mujeres jóvenes (RM=1.30; IC95% 1.09,1.54), escolaridad (RM=1.89; IC95% 1.14,3.12), soltera(o) (RM= 1.31; IC95% 1.24,1.38), desempleo (RM= 2.33; IC95% 2.21,2.45), distanciamiento social (RM 1.81; IC95%1.68,1.96), vivir solo (RM 1.18; IC95% 1.10,1.27), pérdida de familiar por Covid-19 (RM= 1.41; IC95%1.30,1.54), tener un diagnóstico de depresión (RM= 5.72; IC95% 5.41,6.05), ser víctima de violencia física (RM=2.71; IC95% 2.49,2.95), consumo excesivo de alcohol (RM=1.68; IC95%1.58,1.79) y drogas (RM= 3.13; IC95% 2.88,3.41), y sospecha o diagnóstico de Covid-19 (RM=1.79; IC95% 1.67,1.89). CONCLUSIONES: La prevalencia de IS durante la pandemia por Covid-19 fue elevada; se discute la relevancia de los DS estructurales e intermedios que influyen en la IS.
COVID-19 , Suicidal Ideation , Humans , Mexico , Pandemics , Social Determinants of Health , Retrospective Studies
Skeletal muscle repair is accomplished by satellite cells (MuSCs) in cooperation with interstitial stromal cells (ISCs), but the relationship between the function of these cells and the metabolic state of myofibers remains unclear. This study reports an altered proportion of MuSCs and ISCs (including adipogenesis-regulatory cells; Aregs) induced by the transgenic overexpression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the myofibers (MCK-PGC-1α mice). Although PGC-1α-driven increase of MuSCs does not accelerate muscle regeneration, myogenic progenitors isolated from MCK-PGC-1α mice and transplanted into intact and regenerating muscles are more prone to fuse with recipient myofibers than those derived from wild-type donors. Moreover, both young and aged MCK-PGC-1α animals exhibit reduced perilipin-positive areas when challenged with an adipogenic stimulus, demonstrating low propensity to accumulate adipocytes within the muscle. Overall, these results unveil that increased PGC-1α expression in the myofibers favors pro-myogenic and anti-adipogenic cell populations in the skeletal muscle.
PURPOSE: To investigate the macular and circumpapillary retinal microvasculature across all stages of Leber hereditary optic neuropathy (LHON) using swept source optical coherence tomography angiography (OCTA). METHODS: This prospective, multicentre, cross-sectional, observational study analysed a total of 119 eyes of 60 patients with molecularly confirmed LHON across all stages and 120 eyes of 60 control subjects. Optical coherence tomography angiography maps centred on the fovea and optic disc were obtained to measure vessel densities (VDs) in the macular superficial (SCP) and deep (DCP) capillary plexuses, and the radial peripapillary capillary plexus (RPCP) respectively. RESULTS: In asymptomatic eyes, only the SCP showed significant changes on average (B coefficient = -0.72, 95% CI = -1.34 to -0.10, p = 0.022) or in sectors representing the papillomacular bundle (PMB) (B coefficient = -1.17, 95% CI = -2.23 to -0.11, p = 0.031). However, in chronic eyes, the greatest magnitude of change was found in the temporal sector of the RPCP (B coefficient = -12.36, 95% CI = -14.49 to -10.23, p < 0.001). The RPCP showed the strongest correlations with visual acuity (VA, logarithm of the minimum angle of resolution; R = -0.677, p < 0.001) and structural parameters (R = 0.747, p < 0.001). CONCLUSIONS: Retinal VD changes in the circumpapillary region of the PMB appear later than in the macula but end up being more profound and correlate better with VA and structural parameters. Further studies are needed to assess the clinical utility of retinal VDs as potential LHON biomarkers.
Optic Atrophy, Hereditary, Leber , Optic Disk , Humans , Tomography, Optical Coherence/methods , Fluorescein Angiography/methods , Optic Atrophy, Hereditary, Leber/diagnosis , Cross-Sectional Studies , Prospective Studies , Retinal Vessels , Optic Disk/blood supply
ABSTRACT: Clinical uses of radiopharmaceuticals imply the administration of radioactive substances that are mainly excreted through urine. The Nuclear Medicine Department at the Instituto Nacional de Cancerología (INC-COL) in Bogota, Colombia, administers radiopharmaceuticals for diagnostics and treatment to many patients, resulting in tens of cubic meters of radioactive waste water (WW) every day. As Colombian regulatory limits for liquid radioactive discharges to the sewer system are lower than in other countries, longer WW decay times are required, even when an in-house waste water treatment plant (WWTP) is used. To fulfill the requirements for controlled disposal of radioactive discharges, a complementary abatement system was implemented to retain WW for periods as long as 360 d, and was connected to the hospital´s WWTP. These holding times can cause major changes in the WW physicochemical parameters, reaching levels higher than acceptable. In this study, we evaluate the decontamination and decay efficiency of the retention system using water quality parameters and the amount of radioactivity in the effluents stored in the tanks and the WWTP. According to the results, to maintain the physicochemical parameters below acceptable levels, biological and chemical treatment of decayed WW is necessary before discharging it into urban waste water. Using the principles of dilution, retention, and decay, an integral radioactive WW management system was implemented favoring the quality of discharges and activity levels to the sewer system, with efficiencies close to 100% for WW from discharges in diagnostic procedures ranging from 98% (131I) to 100% (177Lu) for WW from discharges in therapeutic procedures. Activity concentration assessment in medically-derived radionuclides using an in-house waste water treatment plant (WWTP) and a complementary abatement system; an in-house WWTP could be used as an abatement system for short-lived radionuclides; and a tank-based abatement system attached to the in-house WWTP showed higher efficiencies for long-lived radionuclides and adequate physicochemical parameters for the discharge to the city sewage system.
Nuclear Medicine , Radioactive Waste , Humans , Iodine Radioisotopes/therapeutic use , Radioactive Waste/analysis , Wastewater
Introducción: la pandemia de COVID-19 originó pérdidas humanas, tensiones en la atención médica, la economía y otros sistemas sociales. Objetivo: recopilar información sobre seguridad alimentaria y fortificación de alimentos a base de pulpa de café considerando que una buena nutrición contrarresta las infecciones. Metodología: se analizó literatura en las bases SciELO y SCOPUS restringiendo términos de búsqueda a: seguridad alimentaria, COVID-19, tecnología de bloques o blockchain, suministro alimenticio, micronutrientes, regulación, fortificación con hierro con énfasis en productos a base de pulpa de café. Resultados: en tiempos de pandemia y otros desastres, uno de los factores que afectan la respuesta de un huésped al virus es la nutrición, la seguridad alimentaria es importante especialmente en países con altas tasas de desnutrición y anemia, por ende, es fundamental la fortificación de alimentos comunes para contribuir en garantizar la adecuación nutricional como parte de las respuestas de los gobiernos, especialmente en áreas rurales y urbanas empobrecidas, planteándose sistemas de suministro de alimentos con la tecnología de bloques o blockchain. Conclusión: la fortificación de productos alimenticios a base de pulpa de café y el suministro que aplique tecnología de bloques podría ser una estrategia de respuesta a las consecuencias de la pandemia
SUMMARY Introduction: The COVID-19 pandemic caused human losses, tensions in medical care, the economy and other social systems. Objective: To collect information on food safety and fortification of foods based on coffee pulp, considering that good nutrition counteracts infections. Methodology: Literature in SciELO and SCOPUS bases was analyzed, restricting search terms to food safety, COVID-19, block chain technology, food supply, micronutrients, regulation, iron fortification with emphasis on coffee pulp-based products. Results: In times of pandemic and other disasters, one of the factors that affect the response of a host to the virus is nutrition. The importance of food security is recognized with proposals especially in countries with high rates of malnutrition and anemia, for the fortification of common foods to contribute to guaranteeing nutritional adequacy as part of the governments' responses, especially in impoverished rural and urban areas, considering food supply systems with block or Block Chain technology. Conclusion: The fortification of food products based on coffee pulp and their supply using block chain could be a response strategy to the consequences of the pandemic.
Introdução: a pandemia de COVID-19 causou perdas humanas, tensões na assistência médica, na economia e em outros sistemas sociais. Objetivo: coletar informações sobre segurança alimentar e fortificação de alimentos à base de polpa de café, considerando que uma boa nutrição combate infecções. Metodologia: a literatura foi analisada nas bases de dados SciELO e SCOPUS, restringindo os termos de busca a: segurança alimentar, COVID-19, tecnologia de bloco ou blockchain, abastecimento de alimentos, micronutrientes, regulação, fortificação de ferro com ênfase em produtos à base de polpa de café. Resultados: em tempos de pandemia e outros desastres, um dos fatores que afeta a resposta de um hospedeiro ao vírus é a nutrição, a segurança alimentar é importante principalmente em países com altos índices de desnutrição e anemia, portanto, a fortificação é essencial dos alimentos comuns para ajudar a garantir a adequação nutricional como parte das respostas governamentais, especialmente em áreas rurais e urbanas empobrecidas, considerando sistemas de abastecimento de alimentos com tecnologia block ou blockchain. Conclusão: a fortificação de produtos alimentícios à base de polpa de café e abastecimento aplicando tecnologia de blocos pode ser uma estratégia de resposta às consequências da pandemia.
BACKGROUND: Cachexia, a syndrome frequently occurring in cancer patients, is characterized by muscle wasting, altered energy and protein metabolism and impaired myogenesis. Tumour-derived microvesicles (TMVs) containing proteins, messenger RNAs (mRNAs), and non-coding RNAs could contribute to cancer-induced muscle wasting. METHODS: Differential ultracentrifugation was used to isolate TMVs from the conditioned medium of Lewis lung carcinoma and C26 colon carcinoma cell cultures. TMVs were added to the culture medium of C2C12 myoblasts and myotubes for 24-48-72 h, and the effects on protein and energy metabolism were assessed. TMVs were also isolated from the blood of C26-bearing mice. MicroRNA (miR) profile of TMVs was obtained by RNA-seq and validated by digital drop PCR. Selected miRs were overexpressed in C2C12 myoblasts to assess the effects on myogenic differentiation. RESULTS: Differentiation was delayed in C2C12 myoblasts exposed to TMVs, according to reduced expression of myosin heavy chain (MyHC; about 62% of controls at Day 4) and myogenin (about 68% of controls at Day 4). As for myotubes, TMVs did not affect the expression of MyHC, while revealed able to modulate mitochondria and oxidative metabolism. Indeed, reduced mRNA levels of PGC-1α (C = 1 ± 0.2, TMV = 0.57 ± 0.06, normalized fold change, P < 0.05) and Cytochrome C (C = 1 ± 0.2, TMV = 0.65 ± 0.04, normalized fold change, P < 0.05), associated with increased BNIP3 expression (C = 1 ± 0.1, TMV = 1.29 ± 0.2, normalized fold change, P < 0.05), were observed, suggesting reduced mitochondrial biogenesis/amount and enhanced mitophagy. These changes were paralleled by decreased oxygen consumption (C = 686.9 ± 44 pmol/min, TMV = 552.25 ± 24 pmol/min, P < 0.01) and increased lactate levels (C = 0.0063 ± 0.00045 nmol/µL, TMV = 0.0094 ± 0.00087 nmol/µL, P < 0.01). A total of 118 miRs were found in MVs derived from the plasma of the C26 hosts; however, only three of them were down-regulated (RNA-seq): miR-181a-5p (-1.46 fold change), miR-375-3p (-2.52 fold change), and miR-455-5p (-3.87 fold change). No correlation could be observed among miRs in the MVs obtained from the blood of the C26 host and those released by C26 cells in the culture medium. Overexpression of miR-148a-3p and miR-181a-5p in C2C12 myoblasts revealed the ability to impinge on the mRNA levels of Myf5, Myog, and MyHC (Myh4 and Myh7). CONCLUSIONS: These results show that in C2C12 cultures, TMVs are able to affect both differentiation and the mitochondrial system. Such effects could be related to TMV-contained miRs.
Extracellular Vesicles , MicroRNAs , Neoplasms , Animals , Cell Line , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle, Skeletal/metabolism , Myoblasts/metabolism , Neoplasms/metabolism
Resumen OBJETIVO: Identificar las causas, curso clínico y el desenlace de las pacientes con estancia prolongada en la unidad de cuidados intensivos de un centro de atención ginecoobstétrica de tercer nivel. MATERIALES Y MÉTODOS: Estudio retrolectivo, transversal y descriptivo de serie de casos llevado a cabo en la unidad de cuidados intensivos de la Unidad Médica de Alta Especialidad Hospital de Ginecoobstetricia 3 del Centro Médico Nacional La Raza del Instituto Mexicano del Seguro Social, Ciudad de México, en pacientes admitidas entre enero de 2016 y diciembre de 2019. Solo se consultaron los expedientes de las pacientes con estancia prolongada definida: tiempo en días, con dos desviaciones estándar por encima de la media general. Se estudiaron los motivos de ingreso, causas que condicionaron la estancia prolongada y el desenlace. RESULTADOS: Se estudiaron 34 pacientes con estancia prolongada que representaron el 2.23% del total de casos de la unidad de cuidados intensivos. Motivos de ingreso: complicaciones del embarazo 20 de 34, complicaciones de la cirugía del aparato genitourinario 7 de 34 y también 7 de 34 con complicaciones quirúrgicas de tumores malignos pelvi-abdominales. La estancia prolongada en la unidad de cuidados intensivos, en promedio, fue de 11.99 ± 4.21 días, condicionada por reintervenciones por sangrado en 9 de 34 pacientes, lesión renal aguda 7 de 34, insuficiencia multiorgánica 5 de 34, descontrol hipertensivo 4 de 34, reintervenciones por infección 3 de 34, desempaquetamiento 3 de 34, ventilación mecánica 2 de 34 y cetoacidosis diabética 1 de 34. Dos pacientes fallecieron (hemorragia intraoperatoria urogenital n = 1 y sepsis de partida abdominal n = 1). CONCLUSIONES: Los casos con estancia prolongada representaron un pequeño porcentaje, las principales causas fueron multifactoriales y la frecuencia de mortalidad fue baja.
Abstract OBJECTIVE: To identify the causes, clinical course and outcome of patients with prolonged stay in the intensive care unit of a third level gyneco-obstetric care center. MATERIALS AND METHODS: Retrolective, cross-sectional, descriptive case series study conducted in the intensive care unit of the Unidad Médica de Alta Especialidad Hospital de Gineco-Obstetricia 3 del Centro Médico Nacional La Raza del Instituto Mexicano del Seguro Social, Mexico City, in patients admitted between January 2016 and December 2019. Only the records of patients with defined prolonged stay were consulted: time in days, with two standard deviations above the overall mean. We studied the reasons for admission, causes that conditioned the prolonged stay and the outcome. RESULTS: Thirty-four patients with prolonged stay were studied, representing 2.23% of the total number of cases in the intensive care unit. Reasons for admission: pregnancy complications 20 out of 34, complications of genitourinary system surgery 7 out of 34 and also 7 out of 34 with surgical complications of pelvi-abdominal malignant tumors. Prolonged stay in the intensive care unit, on average, was 11.99 ± 4.21 days, conditioned by reinterventions for bleeding 9 of 34, acute kidney injury 7 of 34, multiorgan failure 5 of 34, hypertensive decontrol 4 of 34, reinterventions for infection 3 of 34, unpacking 3 of 34, mechanical ventilation 2 of 34 and diabetic ketoacidosis 1 of 34. Mortality occurred in 2 cases (urogenital intraoperative bleeding n = 1 and abdominal game sepsis n = 1). CONCLUSIONS: Cases with prolonged length of stay represented a small percentage, the main causes were multifactorial, and the frequency of mortality was low.
BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.
Optic Atrophy, Hereditary, Leber/drug therapy , Ubiquinone/analogs & derivatives , Visual Acuity , Adolescent , Adult , Aged , Antioxidants/therapeutic use , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Optic Atrophy, Hereditary, Leber/physiopathology , Retrospective Studies , Time Factors , Treatment Outcome , Ubiquinone/therapeutic use , Young Adult
Recent Surface Force Apparatus measurements on thin film drainage as a bubble approaches a surface are reinterpreted in terms of a new model for the air/water interface. In this model, surface charge at the interface can be convected and can diffuse along the surface as the film drains. This creates surface tension gradients, since surface tension includes a charge-dependent contribution from the double-layer free energy. Although this electrocapillary effect is relatively small, we show here that the gradients are large enough to create Marangoni effects that influence the hydrodynamic flow in real systems. The new model can account for observed changes in hydrodynamic boundary condition from mobile initially to immobile during early stages of film drainage, and back to partially mobile as drainage progresses. Experimental film profiles for a millimeter-size bubble in 1 mM KCl solution driven toward a mica surface at 27 µm/s are reasonably well described with this mobile surface charge model. At longer times, there are still features of the experimental data that remain to be explained, which suggests further modeling is warranted.
BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.
Glomerulonephritis, IGA , Adult , Aged , Female , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/epidemiology , Glomerulonephritis, IGA/therapy , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Treatment Outcome
The management of cancer patients is frequently complicated by the occurrence of cachexia. This is a complex syndrome that markedly impacts on quality of life as well as on tolerance and response to anticancer treatments. Loss of body weight, wasting of both adipose tissue and skeletal muscle and reduced survival rates are among the main features of cachexia. Skeletal muscle wasting has been shown to depend, mainly at least, on the induction of protein degradation rates above physiological levels. Such hypercatabolic pattern is driven by overactivation of different intracellular proteolytic systems, among which those dependent on ubiquitin-proteasome and autophagy. Selective rather than bulk degradation of altered proteins and organelles was also proposed to occur. Within the picture described above, the muscle is frequently considered a sort of by-stander tissue where external stimuli, directly or indirectly, can poise protein metabolism toward a catabolic setting. By contrast, several observations suggest that the muscle reacts to the wasting drive imposed by cancer growth by activating different compensatory strategies that include anabolic capacity, the activation of autophagy and myogenesis. Even if muscle response is eventually ill-fated, its occurrence supports the idea that in the presence of appropriate treatments the development of cancer-induced wasting might not be an ineluctable event in tumor hosts.
The interfacial behavior of surfactants present in a natural extract from Quillaja saponaria Molina bark at the air-solution interface is studied by measurements of interfacial tension, interfacial elasticity, and interfacial reflectance FTIR spectroscopy. The active molecule, saponin, is observed directly at the air-solution interface (via reflectance FTIR spectroscopy) above and below the pKa of the molecule, and spectra confirm the altered charge of the interfacial layer at the two solution conditions. For all concentrations of saponin studied, and at pH values below and above pKa (i.e. pH 3 and 7), a reduction in interfacial tension as a function of time is observed, with some differences in early time-scale adsorption and with lower values of quasi-equilibrium interfacial tension for pH 3. The interfacial layer is seen to be elastic, as determined from measurements of hydrostatic expansion, with some variation at the two pH values, and as a function of concentration. In addition to interfacial layer characterisation, the interaction between two air-solution interfaces is probed using bubble collisions with an air-solution interface. This experiment allows for observation of thin film drainage kinetics and determination of the final foam film thickness for the case when one of the interfaces is at equilibrium while the dynamic adsorption layer is being established at the other. This is the first time when the interactions between such interfaces (i.e. only one being at equilibrium) have been studied. This is of particular importance for the formation stage of foams, during which time many of the interfaces are not at equilibrium. When two interfaces interact across a thin liquid film, pH is seen to significantly influence foam film thickness.
Plant Bark/chemistry , Quillaja/chemistry , Saponins/analysis , Hydrogen-Ion Concentration , Rheology , Solutions , Spectroscopy, Fourier Transform Infrared , Surface Tension
Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis. Identification of inherited complement abnormalities explained nine of the 22 cases, with CFH mutations and CFH to CFHR1 gene conversion events being the most prevalent genetic alterations associated with this disorder (66%). In thirteen of the cases, pregnancy complications were sufficient to trigger a thrombotic microangiopathy in the absence of genetic or acquired complement alterations. The postpartum period was the time with highest risk to develop the disease and the group shows an association of cesarean section with pregnancy-associated aHUS. Seventeen patients underwent plasma treatments with a positive renal response in only three cases. In contrast, ten patients received eculizumab with an excellent renal response in all, independent of carrying or not inherited complement abnormalities. Although the cohort is relatively small, the data suggest that pregnancy-associated aHUS is not different from other types of aHUS and suggest the efficacy of eculizumab treatment over plasma therapies. This study may be useful to improve prognosis in this group of aHUS patients.
Atypical Hemolytic Uremic Syndrome , Pregnancy Complications , Thrombotic Microangiopathies , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Atypical Hemolytic Uremic Syndrome/epidemiology , Atypical Hemolytic Uremic Syndrome/genetics , Atypical Hemolytic Uremic Syndrome/immunology , Atypical Hemolytic Uremic Syndrome/therapy , Cesarean Section , Complement Activation , Complement C3b Inactivator Proteins/genetics , Complement Factor H/genetics , Female , Gene Conversion , Humans , Immunosuppressive Agents/therapeutic use , Mutation , Parity , Plasma Exchange , Postpartum Period , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Complications/genetics , Pregnancy Complications/immunology , Pregnancy Complications/therapy , Registries , Renal Dialysis , Retrospective Studies , Risk Factors , Spain/epidemiology , Thrombotic Microangiopathies/epidemiology , Thrombotic Microangiopathies/genetics , Thrombotic Microangiopathies/immunology , Thrombotic Microangiopathies/therapy , Treatment Outcome
Surface and hydrodynamic forces acting between an air bubble and a flat mica surface in surfactant-free water and in 1 mM KCl solution have been investigated by observing film drainage using a modified surface force apparatus (SFA). The bubble shapes observed with the SFA are compared to theoretical profiles computed from a model that considers hydrodynamic interactions, surface curvature, and disjoining pressure arising from electrical double layer and van der Waals interactions. It is shown that the bubble experiences double-layer forces, and a final equilibrium wetting film between the bubble and mica surfaces is formed by van der Waals repulsion. However, comparison with the theoretical model reveals that the double-layer forces are not simply a function of surface separation. Rather, they appear to be changed by one of more of the following: the bubble's dynamic deformation, its proximity to another surface, and/or hydrodynamic flow in the aqueous film that separate them. The same comments apply to the hydrodynamic mobility or immobility of the air-water interface. Together the results show that the bubble's surface is "soft" in two senses: in addition to its well-known deformability, its local properties are affected by weak external forces, in this case the electrical double-layer interactions with a nearby surface and hydrodynamic flow in the neighboring aqueous phase.
