Cognitive Impairment Related to Chronic Kidney Disease Is Associated with a Decreased Abundance of Membrane-Bound Klotho in the Cerebral Cortex.

Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes in cognitive function and the levels of Klotho in the brain cortex in an experimental model of CKD. To induce renal damage, Wistar rats received a diet containing 0.25% adenine for six weeks, while the control group was fed a standard diet. The animals underwent different tests for the assessment of cognitive function. At sacrifice, changes in the parameters of mineral metabolism and the expression of Klotho in the kidney and frontal cortex were evaluated. The animals with CKD exhibited impaired behavior in the cognitive tests in comparison with the rats with normal renal function. At sacrifice, CKD-associated mineral disorder was confirmed by the presence of the expected disturbances in the plasma phosphorus, PTH, and both intact and c-terminal FGF23, along with a reduced abundance of renal Klotho. Interestingly, a marked and significant decrease in Klotho was observed in the cerebral cortex of the animals with renal dysfunction. In sum, the loss in cerebral Klotho observed in experimental CKD may contribute to the cognitive dysfunction frequently observed among patients. Although further studies are required, Klotho might have a relevant role in the development of CKD-associated CI and represent a potential target in the management of this complication.

On spillovers in economic evaluations: definition, mapping review and research agenda.

An important issue in economic evaluations is determining whether all relevant impacts are considered, given the perspective chosen for the analysis. Acknowledging that patients are not isolated individuals has important implications in this context. Increasingly, the term "spillovers" is used to label consequences of health interventions on others. However, a clear definition of spillovers is lacking, and as a result, the scope of the concept remains unclear. In this study, we aim to clarify the concept of spillovers by proposing a definition applicable in health economic evaluations. To illustrate the implications of this definition, we highlight the diversity of potential spillovers through an expanded impact inventory and conduct a mapping review that outlines the evidence base for the different types of spillovers. In the context of economic evaluations of health interventions, we define spillovers as all impacts from an intervention on all parties or entities other than the users of the intervention under evaluation. This definition encompasses a broader range of potential costs and effects, beyond informal caregivers and family members. The expanded impact inventory enables a systematic approach to identifying broader impacts of health interventions. The mapping review shows that the relevance of different types of spillovers is context-specific. Some spillovers are regularly included in economic evaluations, although not always recognised as such, while others are not. A consistent use of the term "spillovers", improved measurement of these costs and effects, and increased transparency in reporting them are still necessary. To that end, we propose a research agenda.

Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis.

Iron overload caused by hereditary hemochromatosis (HH) increases free reactive oxygen species that, in turn, induce lipid peroxidation. Its 4-hydroxynonenal (HNE) by-product is a well-established marker of lipid peroxidation since it reacts with accessible proteins with deleterious consequences. Indeed, elevated levels of HNE are often detected in a wide variety of human diseases related to oxidative stress. Here, we evaluated HNE-modified proteins in the membrane of erythrocytes from HH patients and in organs of Hfe-/- male and female mice, a mouse model of HH. For this purpose, we used one- and two-dimensional gel electrophoresis, immunoblotting and MALDI-TOF/TOF analysis. We identified cytoskeletal membrane proteins and membrane receptors of erythrocytes bound to HNE exclusively in HH patients. Furthermore, kidney and brain of Hfe-/- mice contained more HNE-adducted protein than healthy controls. Our results identified main HNE-modified proteins suggesting that HH favours preferred protein targets for oxidation by HNE.

Prevalence of Depression and Related Factors among Patients with Chronic Disease during the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

The management of chronic diseases in the midst of the COVID-19 pandemic is especially challenging, and reducing potential psychological harm is essential. This review aims to determine the prevalence of depression during the COVID-19 pandemic in patients with chronic disease, and to characterize the impacts of related factors. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The meta-analysis was performed using StatsDirect software. The review identified 33 articles with a total of 50,905 patients with chronic diseases. Four meta-analyses were performed to estimate the prevalence of depression. In diabetic patients, the prevalence ranged from 17% (95% CI = 7-31) (PHQ-9) to 33% (95% CI = 16-51) (PHQ-8); in obese patients, the prevalence was 48% (95% CI = 26-71); and in hypertensive patients, the prevalence was 18% (95% CI = 13-24). The factors significantly associated with depression were female sex, being single, deterioration in the clinical parameters of diabetes, a decrease in self-care behavior, reduced physical activity and sleep time and fear of contagion. The COVID-19 pandemic has significantly increased levels of depression among persons with chronic disease. Pandemics and other emergency events have a major impact on mental health, so early psychological interventions and health management policies are needed to reinforce chronic patients' physical and mental health.

Continuity of Nursing Care in Patients with Coronary Artery Disease: A Systematic Review.

Coronary artery disease is the leading cause of death worldwide and patient continuity of care is essential. Health professionals can help in the transition stage by providing resources to achieve pharmacological treatment adherence, as well as social and emotional support. The objective was to analyse the effects of nursing interventions based on continuity of care in patients with coronary artery disease after hospital discharge. A systematic review of randomised controlled trials and quasi-experimental studies was carried out. Cochrane, CINAHL, Health & medical collection, Medline, and Scopus databases were consulted in January 2022. PRISMA guidelines were followed with no time limits. In total, 16 articles were included with a total of 2950 patients. Nurse-led continuity of care programs improved the monitoring and control of the disease. Positive effects were found in the quality of life of patients, and in mental health, self-efficacy, and self-care capacity dimensions. Clinical parameters such as blood pressure and lipid levels decreased. The continuity of care provided by nurses had a positive influence on the quality of life of patients with coronary artery disease. Nurse-led care focused on the needs and resources, including continuity of care, plays a key role.

Spontaneous Haematomas in Anticoagulated Covid-19 Patients: Diagnosis and Treatment by Embolization.

PURPOSE: To assess the safety and efficacy of embolization for spontaneous bleeding in anticoagulated patients with COVID-19. MATERIAL AND METHODS: Single center retrospective study in 9 patients with COVID-19 who experienced bleeding complications following anticoagulation. The study included 8 men and 1 woman aged from 48 to 80 years (mean 69.7 years), who had a total of 10 soft tissue haematomas: 1 in the thigh, 1 in the anterior abdominal wall, 6 retroperitoneal and 2 thoracic haematomas. All patients were referenced for vascular embolization, mostly with Onyx-18. RESULTS: A total of 10 haematomas were embolized in 9 patients. Technical success was achieved in all patients. No complications or adverse events were noted. One patient required percutaneous drainage of an infected haematoma 88 days after embolization. The mean hemoglobin level before embolization was 8,64 mg/dL and increased to 9,08 mg/dL after embolization (p = 0,3). After embolization all patients recovered haemodynamic stability and blood pressure levels improved. Seven patients resumed anticoagulation therapy after embolization. There were no recurrences or new bleedings in all treated patients. No patients required any additional invasive therapies or surgery. Mean intensive unit care and hospital stay was 6.7 and 35.2 days, respectively. All patients were discharged and were well at follow-up clinic visits 2-7 months after embolization. Seven patients performed a control CT scan 1-6 months after embolization, showing complete resolution of the haematoma. CONCLUSION: Embolization is safe and effective to treat spontaneous haematomas in anticoagulated patients with COVID-19, allowing to resume anticoagulation therapy. Level of evidence IV Level 4, case-series.

Effect of a game-based intervention on preoperative pain and anxiety in children: A systematic review and meta-analysis.

BACKGROUND: Games are increasingly being used as a means of alleviating pain and anxiety in paediatric patients, in the view that this form of distraction is effective, non-invasive and non-pharmacological. AIMS: To determine whether a game-based intervention (via gamification or virtual reality) during the induction of anaesthesia reduces preoperative pain and anxiety in paediatric patients. METHODS: A systematic review with meta-analysis of randomised controlled trials was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and using RevMan software. The review was based on a search of the EMBASE, CINAHL, Medline, SciELO and Scopus databases, conducted in July 2021. No restriction was placed on the year of publication. RESULTS: 26 studies were found, with a total study population of 2525 children. Regarding pain reduction, no significant differences were reported. For anxiety during anaesthesia induction, however, a mean difference of -10.62 (95% CI -13.85, -7.39) on the Modified Yale Preoperative Anxiety Scale, in favour of game-based intervention, was recorded. CONCLUSIONS: Game-based interventions alleviate preoperative anxiety during the induction of anaesthesia in children. This innovative and pleasurable approach can be helpful in the care of paediatric surgical patients. RELEVANCE TO CLINICAL PRACTICE: In children, preoperative management is a challenging task for healthcare professionals, and game-based strategies could enhance results, improving patients' emotional health and boosting post-surgery recovery. Distractive games-based procedures should be considered for incorporation in the pre-surgery clinical workflow in order to optimise healthcare.

Pregnancy in teenagers with heart disease / Embarazo en pacientes adolescentes con cardiopatía

Abstract The prevalence of pregnancy in adolescent women is high in Mexico and represents a public health problem. The pregnant teenager with heart disease has a high probability of complications during pregnancy and the delivery, which carries a risk of death of both the mother and the product. In many cases the pregnancy should have been avoided, planned or interrupted, however the majority at this age is vulnerable and although certain cases must be interrupted by their high risk of maternal-fetal death, prevention and legal aspects should be considered. In some cases the woman wants a pregnancy although her health condition does not allow it, but there are options of adoption or recourse to a surrogate belly. In response to this growing social problem, the National Cardiology Institute Ignacio Chávez and National Institute of Perinatology, with the coordination of Ministry of Health in Mexico, started a pregnancy prevention module within a clinic of follow-up of cardiopathy and pregnancy. This review raises the global problem in our country that occupies the first place in pregnancies in adolescents, with more than 400,000 pregnancies a year and the form of immediate response in a multidisciplinary way.

Resumen La prevalencia de embarazo en mujeres adolescentes es muy alta en México, y representa un problema de salud pública. La adolescente embarazada con cardiopatía tiene altas posibilidades de complicaciones durante el embarazo y su resolución, lo que pone en riesgo la vida tanto de la madre como del producto. En muchos casos el embarazo debió ser evitado, planeado o interrumpido, sin embargo la mayoría a esta edad es vulnerable y si bien ciertos casos deben ser interrumpidos por su alto riesgo de muerte materno-fetal, es fundamental considerar la prevención y los aspectos legales. En algunos casos la mujer desea un embarazo aunque su condición de salud no se lo permite, pero existen opciones de adopción o recurrir a un vientre subrogado. Atendiendo este problema social cada vez más creciente, el Instituto Nacional de Cardiología Ignacio Chávez, en coordinación con la Comisión Coordinadora de la Secretaría de Salud y el Instituto Nacional de Perinatología, echaron a andar un módulo de prevención de embarazo dentro de una clínica de seguimiento de cardiopatía y embarazo. Esta revisión plantea el problema global en nuestro país, que ocupa el primer lugar en embarazos en adolescentes, con más de 400 mil embarazos al año y la forma de dar respuesta inmediata de manera multidisciplinaria.

Pregnancy in teenagers with heart disease.

The prevalence of pregnancy in adolescent women is high in Mexico and represents a public health problem. The pregnant teenager with heart disease has a high probability of complications during pregnancy and the delivery, which carries a risk of death of both the mother and the product. In many cases the pregnancy should have been avoided, planned or interrupted, however the majority at this age is vulnerable and although certain cases must be interrupted by their high risk of maternal-fetal death, prevention and legal aspects should be considered. In some cases the woman wants a pregnancy although her health condition does not allow it, but there are options of adoption or recourse to a surrogate belly. In response to this growing social problem, the National Cardiology Institute Ignacio Chávez and National Institute of Perinatology, with the coordination of Ministry of Health in Mexico, started a pregnancy prevention module within a clinic of follow-up of cardiopathy and pregnancy. This review raises the global problem in our country that occupies the first place in pregnancies in adolescents, with more than 400,000 pregnancies a year and the form of immediate response in a multidisciplinary way.

La prevalencia de embarazo en mujeres adolescentes es muy alta en México, y representa un problema de salud pública. La adolescente embarazada con cardiopatía tiene altas posibilidades de complicaciones durante el embarazo y su resolución, lo que pone en riesgo la vida tanto de la madre como del producto. En muchos casos el embarazo debió ser evitado, planeado o interrumpido, sin embargo la mayoría a esta edad es vulnerable y si bien ciertos casos deben ser interrumpidos por su alto riesgo de muerte materno-fetal, es fundamental considerar la prevención y los aspectos legales. En algunos casos la mujer desea un embarazo aunque su condición de salud no se lo permite, pero existen opciones de adopción o recurrir a un vientre subrogado. Atendiendo este problema social cada vez más creciente, el Instituto Nacional de Cardiología Ignacio Chávez, en coordinación con la Comisión Coordinadora de la Secretaría de Salud y el Instituto Nacional de Perinatología, echaron a andar un módulo de prevención de embarazo dentro de una clínica de seguimiento de cardiopatía y embarazo. Esta revisión plantea el problema global en nuestro país, que ocupa el primer lugar en embarazos en adolescentes, con más de 400 mil embarazos al año y la forma de dar respuesta inmediata de manera multidisciplinaria.

Embolismo arterial gaseoso paradójico tras una herida incisa craneal directa / Paradoxical arterial gas embolism following a direct incisive injury to the skull

Introducción. El embolismo arterial gaseoso se define como la presencia de aire en la circulación arterial. Se trata de una causa extremadamente rara de ictus que se ha descrito en multitud de escenarios clínicos, generalmente relacionados con procesos yatrógenos. Se aporta un caso clínico en el que el embolismo arterial gaseoso sucedió tras un traumatismo craneoencefálico, y se revisan los aspectos más relevantes del diagnóstico y la etiopatogenia. Caso clínico. Mujer de 52 años que presentaba herida incisa craneofacial tras una agresión con un hacha. La tomografía computarizada inicial objetivó fractura en los arcos cigomático, esfenoidal y maxilar izquierdos, así como neumoencéfalo en los senos cavernosos y el canal carotídeo derecho. Una hora más tarde, la paciente mostró un déficit neurológico hemisférico derecho, por lo que se solicitó de forma urgente una nueva tomografía computarizada craneal con estudio vascular multimodal, que objetivó la movilización del neumoencéfalo y descartó una oclusión arterial de gran vaso. Un estudio de shunt mediante Doppler transcraneal y ecocardiografía comprobó la presencia de un foramen oval permeable como causa de comunicación arteriovenosa que justificaba un embolismo arterial gaseoso. La tomografía computarizada de control a las 48 horas confirmó la aparición de una lesión isquémica parietal derecha. Conclusión. En este caso queda reflejada la presencia simultánea de aire en la circulación cerebral arterial y venosa y la comunicación periférica a través de un foramen oval permeable. Este mecanismo de producción está escasamente documentado en la bibliografía

Introduction. An arterial gas embolism is defined as the presence of air in the arterial circulation. This is an extremely rare cause of stroke that has been described in a multitude of clinical scenarios, generally related to iatrogenic processes. A clinical case is reported in which the arterial gas embolism occurred after a traumatic brain injury, and the most relevant aspects of diagnosis and aetiopathogenesis are reviewed. Case report. We report the case of a 52-year-old woman with an open craniofacial wound resulting from an attack with an axe. The initial CT scan found fractures in the left zygomatic, sphenoidal and maxillary arches, as well as pneumocephalus in the cavernous sinuses and the right carotid canal. One hour later, the patient showed a neurological deficit in the right hemisphere, and so a new cranial computed tomography scan with multimodal vascular study was urgently requested, which revealed the mobilisation of the pneumocephalus and ruled out a large vessel arterial occlusion. A shunt study using transcranial Doppler and echocardiography showed the presence of a patent foramen ovale to be the cause ofarteriovenous communication that justified an arterial gas embolism. The follow-up CT scan at 48 hours confirmed the appearance of a right parietal ischaemic lesion. Conclusion. This case reflects the simultaneous presence of air in the arterial and venous circulation of the brain, as well as the peripheral communication through a patent foramen ovale. This production mechanism is poorly documented in the literature

Implications of Vitamin D in Multiple Sclerosis and Other Neurodegenerative Processes: Bibliometric Analysis and Systematic Review.

In recent years, numerous investigations focused on the pleiotropic actions of vitamin D have been carried out. These actions include the participation of this molecule in neurophysiological and neuropathological processes. As a consequence, abundant scientific literature on the role of this vitamin in neurodegenerative entities has emerged, even concerning clinical studies. To identify the level of scientific evidence concerning the relation between vitamin D and neurodegenerative diseases, from a quantitative and qualitative perspective. To describe, by means of a bibliometric analysis, the scientific production and its evolution through time in quantitative terms, regarding the implications of vitamin D in neurodegeneration. To analyse and present the degree of evidence in the aforementioned field of study, a systematic review of the literature focused on the most prevalent neurodegenerative diseases was carried out. We retrieved 848 articles in the bibliometric analysis, the majority of which were dated between the years 2010-2017. The most studied metabolite was the 25(OH)D3 and the most cited disease was multiple sclerosis. In the systematic review, we found studies about Alzheimer's and Parkinson's diseases and again, about multiple sclerosis prominently (in number and quality), with 12 randomised double-blind clinical trials. The research about vitamin D and its relations with neurodegenerative diseases shows a growing evolution over the last decade. More studies are needed to find correlations between the clinical severity of these diseases and the specific status of vitamin D and the genotypes related with them, which seems to be a future trend.

Aumento de los depósitos cerebrales de hierro en una familia de donantes de sangre con síndrome de piernas inquietas / Brain iron accumulation in a blood donor family with restless legs síndrome

Introducción. La fisiopatología del síndrome de piernas inquietas (SPI) es compleja. El mecanismo a través del cual la ferropenia favorece el desarrollo del SPI no está esclarecido, aunque se sugiere la presencia de una alteración en la homeostasis cerebral del hierro. Casos clínicos. Se presentan los hallazgos inusuales en una familia de donantes de sangre con SPI. Tres miembros de la misma familia fueron diagnosticados de SPI, cumpliendo los criterios definidos por el grupo internacional para el estudio del SPI (International Restless Legs Syndrome Study Group). Todos eran donantes de sangre habituales (rango de donación: 10-40 años) y los síntomas de SPI tenían un curso de 3-5 años. La exploración general y neurológica fue normal en todos los casos, así como los electromiogramas. El estudio fenotípico y genotípico descartó la presencia de hemocromatosis y otras causas genéticas de sobrecarga cerebral de hierro. Los estudios polisomnográficos mostraron sueño nocturno perturbado, con reducción de su eficiencia, y un aumento del índice de movimientos periódicos de las piernas. La resonancia magnética craneal evidenció un aumento de los depósitos cerebrales de hierro en los ganglios basales, la sustancia negra, el núcleo rojo y los dentados. Conclusión. Este aumento patológico de los depósitos cerebrales de hierro sugiere la presencia de un complejo trastorno del metabolismo cerebral del hierro en nuestros pacientes. Futuros estudios deben confirmar estos hallazgos y profundizar en el estudio de su relación con la fisiopatología del SPI

Introduction. The pathophysiology of restless legs syndrome (RLS) is complex. Secondary RLS with iron deficiency - which suggests disturbed iron homeostasis - remains to be elucidated. Case reports. We report the findings from a unique blood donor family with RLS. Three blood donors family members were diagnosed with RLS defined by the International RLS Study Group and without history of neurologic diseases and RLS symptoms in the last 3-5 years (range of blood donation: 10-40 years). The neurological examination and electromyographies were normal. A polisomnography showed disturbed nocturnal sleep with a reduction in sleep efficiency and an increased periodic limbs movement index. The cranial MRI showed brain iron deposits in basal ganglia, substantia nigra, red nuclei and dentate nuclei. Phenotypic and genotypic studies rule out genetic haemochromatosis or iron overload. Conclusion. The abnormal iron accumulation in the basal ganglia indicated a complex iron metabolism disorder of the central nervous system. Further studies are warranted to confirm our findings and its role in the pathophysiology of RLS

The influence of HE history, HE status and neuropsychological test type on learning ability in patients with cirrhosis.

BACKGROUND & AIMS: Learning ability may be impaired in patients with a history of overt hepatic encephalopathy (OHE). The aim of this study was to compare performance on the first/second attempt at a series of tests. METHODS: Two hundred and fourteen patients with cirrhosis were enrolled. On the day of study, 41% were classed as unimpaired, 38% as having minimal HE and 21% as having mild OHE; 58% had a history of OHE. Performance was compared between two versions of the trail-making test A (TMT-A), and between the first/second half of a simple/choice reaction time (sRT and cRT), and a working memory test (ScanRT). RESULTS: Both patients with and without OHE history improved in TMT-A, sRT and ScanRT. Only patients with no OHE history improved in cRT. All patients, regardless of their HE status on the day of study, improved in TMT-A and sRT. Only patients with mild OHE on the day of study improved in cRT. Only unimpaired patients improved in ScanRT. When OHE history and HE status on the day of study were tested together, only HE status had an effect. The same held true when age, the Model for End Stage Liver Disease (MELD) and educational attainment were adjusted for. CONCLUSIONS: HE status on the day of study and the type of neuropsychological test had an effect on learning ability in a well-characterized group of patients with cirrhosis.

Hidden myelodysplastic syndrome (MDS): A prospective study to confirm or exclude MDS in patients with anemia of uncertain etiology.

INTRODUCTION: Diagnosis of myelodysplastic syndromes (MDSs) when anemia is the only abnormality can be complicated. The aim of our study was to investigate the primary causes of anemia and/or macrocytosis of uncertain etiology. METHODS: We conducted a multicenter, prospective study over 4 months in three hematology laboratories. In step 1, we used an automated informatics system to screen 137 453 hemograms for cases of anemia and/or macrocytosis (n = 2702). In step 2, we excluded all patients whose anemia appeared to be due to a known cause. This left 290 patients had anemia of uncertain etiology. In step 3, we conducted further investigations, including a peripheral blood smear, and analysis of iron, vitamin B12, folate, and thyroid hormone levels. RESULTS: A differential diagnosis was obtained in 139 patients (48%). The primary causes of anemia were iron deficiency (n = 59) and megaloblastic anemia (n = 39). In total, 25 hematologic disorders were diagnosed, including 14 patients with MDS (56%). The median age of MDS patients was 80 years, 12 had anemia as an isolated cytopenia, and most (n = 10) had lower-risk disease (IPSS-R ≤ 3.5). SF3B1 mutations were most frequent (n = 6) and correlated with the presence of ring sideroblasts (100%) and associated with better prognosis (P = 0.001). CONCLUSIONS: Our prospective, four-step approach is an efficient and logical strategy to facilitate the diagnosis of MDS on the basis of unexplained anemia and/or macrocytosis, and may allow the early diagnosis of the most serious causes of anemia. Molecular analysis of genes related to MDS could be a promising diagnostic and prognostic approach.

Fish oil diet in pregnancy and lactation reduces pup weight and modifies newborn hepatic metabolic adaptations in rats.

PURPOSE: To determine the effects of a diet containing fish oil (FD) during pregnancy and lactation in rats on the metabolic adaptations made by the offspring during early extrauterine life and to compare it to an olive oil diet (OD). METHODS: Rats were mated and randomly allocated to OD or FD containing 10 % of the corresponding oil. During lactation, litters were adjusted to eight pups per dam. Fetuses of 20 days and pups of 0, 1, 10, 20 and 30 days of age were studied. RESULTS: Body weight and length were lower in pups of the FD group from birth. The diet, milk, pups' plasma and liver of FD group had higher proportions of n-3 LCPUFA, but the content of arachidonic acid (ARA) was lower. Plasma glucose was higher, but unesterified fatty acids, triacylglycerols (TAG), 3-hydroxybutyrate and liver TAG in 1-day-old pups were lower in the FD group, and differences in some of these variables were also found in pups up to 30 days old. Liver lipoprotein lipase activity and mRNA expression, and the expression of carnitine palmitoyl transferase I, acyl-CoA oxidase and 3-hydroxy 3-methyl glutaryl-CoA synthase increased more at birth in pups of the FD group, but the expression of sterol regulatory element binding protein-1c and Δ6-desaturase mRNA was lower in the FD group. CONCLUSIONS: Maternal intake of high n-3 LCPUFA retards postnatal development, which could be the result of impaired ARA synthesis, and affects hepatic metabolic adaptations to extrauterine life.

Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy.

The management of recurrent/refractory (R/R) Hodgkin lymphoma (HL) remains challenging. Previously published data have shown some efficacy of rituximab in this setting. The purpose of this phase II trial was to investigate the activity of ofatumumab in combination with etoposide, steroids, cytarabine and cisplatin (O-ESHAP) in 62 patients with R/R classical HL. Treatment consisted of ESHAP plus ofatumumab 1000 mg on days 1 and 8 of the first cycle and day 1 of the second and third cycles. O-ESHAP was well tolerated with only 3% of patients requiring treatment discontinuation because of adverse events. Overall response rate was 73% (44% complete metabolic response). In multivariate analysis, early relapse (P < 0·001), bulky disease (P < 0·001) and B symptoms (P < 0·001) were the most important prognostic factors for response. No failures of stem cell mobilization were observed. The high response rate, particularly the complete metabolic response rate, the low toxicity profile, and the high mobilizing potential of the O-ESHAP regimen suggest that patients with R/R HL may benefit from this salvage regimen. However, with the encouraging results observed with other new therapeutic agents in HL, the O-ESHAP regimen could be restricted to patients failing these agents or to those with R/R nodular lymphocyte-predominant HL.

Functional Characterization of Five Protoporphyrinogen oxidase Missense Mutations Found in Argentinean Variegate Porphyria Patients.

A partial deficiency in protoporphyrinogen oxidase (PPOX) produces the acute/cutaneous (or mixed) variegate porphyria (VP), the third most frequent porphyria in Argentina. This autosomal dominant disorder is clinically characterized by skin lesions and/or acute neurovisceral attacks. The precise diagnosis of patients with a symptomatic VP is essential to provide accurate treatment. It is also critical to identify asymptomatic relatives to avoid precipitating factors and prevent acute attacks.Functional consequences of five PPOX missense mutations were evaluated in a prokaryotic expression system. Three mutations were found in families previously reported c.101A>T (p.E34V), c.670T>G (W224G), c.995G>C (G332A) and two were novel findings c.227C>T (p.S76F), c.1265A>G (p.Y422C). All mutations were identified in heterozygotes with reduced PPOX activity and variable clinical expression of the disease, including asymptomatic cases. Prokaryotic expression showed that all five missense mutations decreased the PPOX activity, demonstrating their detrimental effect on enzyme function, and thus, providing evidence for their causative role in VP. These results reinforce the importance of molecular genetic analysis for VP diagnosis and especially the usefulness of prokaryotic expression of missense mutations to assess their deleterious effect on PPOX activity.MM and BXG contributed equally to the publication. RES and MVR share senior authorship.

Nephrotic-range proteinuria in a patient with a giant prolactinoma.

We report for the first time a case of nephrotic-range proteinuria adequately controlled by using dopamine agonists. A 40-year-old man was studied because of persistent asymptomatic nephrotic proteinuria despite lifestyle modifications and treatment with converting enzyme inhibitors. The renal biopsy specimen did not show histopathologic changes. In the follow-up period, a giant prolactinoma was found by chance with extremely high prolactin (PRL) values. After establishing cabergoline therapy, we achieved a remarkable decrease in both serum PRL levels and tumor mass, and surprisingly, proteinuria disappeared. We discuss the possible pathogenic mechanisms of proteinuria that may correspond to PRL level in urine (prolactinuria) or another tumor-related protein.

[Determination of the antioxidant capacity of flavonoids in fruits and fresh and thermicaly treated vegetables]. / Determinación de la capacidad antioxidante de flavonoides en frutas y verduras frescas y tratadas térmicamente.

The main objective of the work was to determine the antioxidant capacity of the flavonoids in red apples with and without skin, strawberries, tomatoes and fresh onions and thermally treated: humid heat (boiled and vapor), dry heat (oven) and high frequency (microwaves). The measurement was carried out in a fluorescence spectroscopy and the statistical analysis through the Variance and Test of Duncan. The results indicate that the antioxidant capacity of the flavonoids of red apples with and without skin, strawberries, tomatoes and onions were of 0.259, 0.267, 0.278, 0.165 and 0.223 Equivalent uM Trolox. These values diminished after the thermal treatment at a higher degree by dry heat at 0.128, 0.072, 0.077 and 0.048 Equivalent uM Trolox respectively and 0.146 Equivalent uM Trolox in the boiled onion. The flavonoids showed a higher antioxidant activity in fresh state, and their activity diminished under heat (cooking).