Detection of SF3B1 p.Lys700Glu Mutation by PNA-PCR Clamping in Myelodysplastic Syndromes and Myeloproliferative Neoplasms.

Mutations in SF3B1 are found in 20% of myelodysplastic syndromes and 5-10% of myeloproliferative neoplasms, where they are considered important for diagnosis and therapy decisions. Sanger sequencing and NGS are the currently available methods to identify SF3B1 mutations, but both are time-consuming and expensive techniques that are not practicable in most small-/medium-sized laboratories. To identify the most frequent SF3B1 mutation, p.Lys700Glu, we developed a novel fast and cheap assay based on PNA-PCR clamping. After setting the optimal PCR conditions, the limit of detection of PNA-PCR clamping was evaluated, and the method allowed up to 0.1% of mutated SF3B1 to be identified. Successively, PNA-PCR clamping and Sanger sequencing were used to blind test 90 DNA from patients affected by myelodysplastic syndromes and myeloproliferative neoplasms for the SF3B1 p.Lys700Glu mutation. PNA-PCR clamping and Sanger sequencing congruently identified 75 negative and 13 positive patients. Two patients identified as positive by PNA-PCR clamping were missed by Sanger analysis. The discordant samples were analyzed by NGS, which confirmed the PNA-PCR clamping result, indicating that these samples contained the SF3B1 p.Lys700Glu mutation. This approach could easily increase the characterization of myelodysplastic syndromes and myeloproliferative neoplasms in small-/medium-sized laboratories, and guide patients towards more appropriate therapy.

Risk Factors for General Anesthesia Conversion in Anterior Circulation Stroke Patients Undergoing Endovascular Treatment.

BACKGROUND AND PURPOSE: No current consensus exists on the best anesthetic management of ischemic stroke patients undergoing mechanical thrombectomy. Both conscious sedation (CS) and general anesthesia (GA) are currently considered valid anesthetic strategies, yet patients managed under CS may require emergent conversion to GA, which has been associated with worse outcomes. The aim of this study was to analyze the conversion rate and potential risk factors for GA conversion during mechanical thrombectomy. METHODS: Two-hundred and twenty-seven patients with consecutive acute anterior circulation ischemic stroke treated with mechanical thrombectomy and initiated under CS or local anesthesia were included in this retrospective analysis. Conversion rate to GA was calculated, while univariate and multivariate analysis were used to identify risk factors. RESULTS: Twenty patients (8.8%) were switched to GA. Multivariate analysis identified procedure duration (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.00-1.02, p value 0.028), tandem stroke (OR 8.57, 95% CI 2.06-35.7, p value 0.003), Sequential Organ Failure Assessment (SOFA) (OR 1.76, 95% CI 1.19-2.61, p value 0.005), and number of pharmacological agents used (OR 5.76, 95% CI 2.49-13.3, p value <0.001) as independently associated with conversion to GA. CONCLUSION: In our study, tandem occlusion, longer endovascular procedures, SOFA, and number of pharmacological agents used predicted the risk of emergent conversion to GA in stroke patients undergoing endovascular treatment. Prospective studies investigating optimal CS strategies are deemed necessary.

[Pulse pressure variation guided fluid therapy during kidney transplantation: a randomized controlled trial]. / Reposição de volume orientada pela variação da pressão de pulso durante transplante renal: estudo randomizado controlado.

PURPOSE: Kidney transplantation is the gold-standard treatment for end stage renal disease. Although different hemodynamic variables, like central venous pressure and mean arterial pressure, have been used to guide volume replacement during surgery, the best strategy still ought to be determined. Respiratory arterial Pulse Pressure Variation (PPV) is recognized to be a good predictor of fluid responsiveness for perioperative hemodynamic optimization in operating room settings. The aim of this study was to investigate whether a PPV-guided fluid management strategy is better than a liberal fluid strategy during kidney transplantation surgeries. Identification of differences in urine output in the first postoperative hour was the main objective of this study. METHODS: We conducted a prospective, single blind, randomized controlled trial. We enrolled 40 patients who underwent kidney transplantation from deceased donors. Patients randomized in the PPV Group received fluids whenever PPV was higher than 12%, patients in the Free Fluid Group received fluids following our institutional standard care protocol for kidney transplantations (10mL.kg-1.h-1). RESULTS: Urinary output was similar at every time-point between the two groups, urea was statistically different from the third postoperative day with a peak at the fourth postoperative day and creatinine showed a similar trend, being statistically different from the second postoperative day. Urea, creatinine and urine output were not different at the hospital discharge. CONCLUSION: PPV-guided fluid therapy during kidney transplantation significantly improves urea and creatinine levels in the first week after kidney transplantation surgery.

Pulse pressure variation guided fluid therapy during kidney transplantation: a randomized controlled trial / Reposição de volume orientada pela variação da pressão de pulso durante transplante renal: estudo randomizado controlado

Abstract Purpose: Kidney transplantation is the gold-standard treatment for end stage renal disease. Although different hemodynamic variables, like central venous pressure and mean arterial pressure, have been used to guide volume replacement during surgery, the best strategy still ought to be determined. Respiratory arterial Pulse Pressure Variation (PPV) is recognized to be a good predictor of fluid responsiveness for perioperative hemodynamic optimization in operating room settings. The aim of this study was to investigate whether a PPV guided fluid management strategy is better than a liberal fluid strategy during kidney transplantation surgeries. Identification of differences in urine output in the first postoperative hour was the main objective of this study. Methods: We conducted a prospective, single blind, randomized controlled trial. We enrolled 40 patients who underwent kidney transplantation from deceased donors. Patients randomized in the "PPV" group received fluids whenever PPV was higher than 12%, patients in the "free fluid" group received fluids following our institutional standard care protocol for kidney transplantations (10 mL.kg-1. h-1). Results: Urinary output was similar at every time-point between the two groups, urea was statistically different from the third postoperative day with a peak at the fourth postoperative day and creatinine showed a similar trend, being statistically different from the second postoperative day. Urea, creatinine and urine output were not different at the hospital discharge. Conclusion: PPV guided fluid therapy during kidney transplantation significantly improves urea and creatinine levels in the first week after kidney transplantation surgery.

Resumo Objetivo: Transplante renal é o tratamento padrão-ouro na doença renal em estágio terminal. Embora diferentes variáveis hemodinâmicas, tais como pressão venosa central e pressão arterial média, têm sido usadas para orientar a estratégia de reposição volêmica durante a cirurgia, a melhor estratégia ainda não foi determinada. A Variação da Pressão de Pulso (VPP) durante o ciclo respiratório é reconhecida como um bom preditor da resposta à infusão de volume para otimização hemodinâmica perioperatória no centro cirúrgico. O objetivo do estudo foi estudar se a estratégia de reposição de volume orientada por VPP é melhor do que a estratégia liberal de reposição de volume durante cirurgia de transplante renal. O principal objetivo do estudo foi identificar diferença no débito urinário na primeira hora do pós-operatório. Método: Realizamos estudo prospectivo, unicego, randomizado, controlado. Incluímos 40 pacientes submetidos a transplante renal de doador cadáver. Pacientes randomizados para o Grupo VPP receberam volume quando a VPP estava acima de 12%, e os pacientes no Grupo Reposição Liberal receberam volume de acordo com o nosso protocolo institucional padrão de assistência para transplante renal (10 mL.kg-1.h-1). Resultados: O débito urinário foi semelhante em todos os tempos nos dois grupos, a ureia foi estatisticamente diferente a partir do terceiro dia do pós-operatório com pico no quarto dia do pós-operatório e a creatinina apresentou tendência semelhante, tornando-se estatisticamente diferente a partir do segundo dia do pós-operatório. Ureia, creatinina e débito urinário não estavam diferentes na alta hospitalar. Conclusões: A terapia orientada por VPP durante transplante renal melhorou de forma significativa os níveis de ureia e creatinina na primeira semana pós-transplante renal.

O narcisismo e a relação com a alteridade nas psicoses sob os olhares de Freud, Tausk e Federn / Narcissism and the relation to otherness in psychoses from the points of view of Freud, Tausk and Federn / Le narcissisme et le rapport à l'altérité chez les psychoses selon Freud, Tausk et Federn / El narcisismo y la relación con la alteridad en las psicosis bajo las miradas de Freud, Tausk y Federn

Este trabalho tem como objetivo analisar a relação ou o lugar da alteridade na dinâmica psíquica das psicoses a partir das ideias de Freud, sobretudo aquelas vinculadas ao conceito de narcisismo, e que influenciaram as teorias de Tausk e Federn, autores que se aventuraram no campo do estudo e tratamento das psicoses no momento em que o próprio pai da psicanálise dizia ser impossível. Deste estudo podemos concluir que a alteridade concreta se fez e se faz presente no psiquismo psicótico para os três autores, de modo que o conflito e o processo terapêutico implicam a existência e a relação com o outro.

This paper analyzes the relation or place of otherness in the psychic dynamics of psychosis based on Freud's ideas, especially those that are related to the concept of narcissism and that influenced the theories developed by Tausk and Federn, authors who ventured in the field of study and treatment of psychosis at a time when the very father of psychoanalysis declared that this was not feasible. We conclude that the concrete otherness occurred and is present in the psychotic psyche according to the three authors, so that the conflict and the therapeutic process imply the existence and the relationship with the other.

Cet article vise à analyser le rapport ou le lieu de l'altération dans la dynamique psychique de la psychose à partir des idées de Freud, en particulier celles liées à la notion de narcissisme et qui ont influencé les théories de Tausk et Federn, auteurs qui se sont aventurés dans le domaine de l'étude et le traitement de la psychose alors que le père même de la psychanalyse jugeait cela irréalisable. Nous concluons que l'altérité concrète s'est opérée et est présente dans la psyché psychotique selon les trois auteurs, de sorte que le conflit et le processus thérapeutique impliquent l'existence et le rapport avec l'autre.

Este artículo pretende analizar la relación o el lugar de la alteridad en la dinámica psíquica de la psicosis a partir de las ideas de Freud, especialmente de aquellas vinculadas al concepto de narcicismo, y que influenciaron a las de Tausk y Federn, autores que se aventuraron en el campo del estudio y del tratamiento de la psicosis en un momento en el que el propio padre del psicoanálisis decía que era imposible. A partir de este estudio, podemos concluir que, para los tres autores, la alteridad concreta se hizo y se hace presente en la psique psicótica, de forma que el conflicto y el proceso terapéutico implican la existencia y la relación con el otro.

Diese Arbeit analysiert die Beziehung oder den Ort der Alterität in der psychischen Dynamik der Psychose, basierend auf Freuds Ideen, die mit dem Konzept des Narzissmus in Verbindung stehen und die Tausk und Federn beeinflusst haben. Diese Autoren haben sich in den Bereich der Studie und Behandlung von Psychosen gewagt und zwar zu einer Zeit, als der Vater der Psychoanalyse behauptete, dass dies ein unmögliches Unterfangen sei. Aus unserer Studie schließen wir, dass die konkrete Alterität in der psychotischen Psyche gemäß diesen Autoren vorhanden ist, so dass der therapeutische Konflikt und Prozess die Existenz des Andern und die Beziehung mit ihm einschließen.

Prophylactic oral nifedipine to reduce preterm delivery: a randomized controlled trial in women at high risk.

OBJECTIVE: To establish the efficacy of prophylactic nifedipine vs. placebo in reducing spontaneous preterm delivery in asymptomatic women at high risk for preterm delivery. DESIGN: Prospective multicentric randomized double-blind study. SETTING: Tertiary care centre, University Hospitals of Brescia and Torino, Italy. POPULATION: Eighty-seven singleton pregnancies without uterine contractions and ultrasonographic cervical length of ≤25 mm at 24-32 weeks, at risk for preterm delivery, with longitudinal follow up in our Preterm Prevention Clinic. METHODS: Selection was done on the basis of ultrasonographic cervical length; 43 women were randomized to receive placebo and 44 to receive nifedipine. MAIN OUTCOME MEASURES: Primary end point: spontaneous preterm delivery <37 weeks in nifedipine vs. placebo. SECONDARY OUTCOMES: delivery <32 weeks, maternal side effects, neonatal complications, admissions to the Neonatal Intensive Care Unit and randomization/delivery time in nifedipine vs. placebo. RESULTS: There was no trend towards a lower risk of spontaneous preterm delivery, neither at <37 weeks of nifedipine vs. placebo (11.4% vs. 19.0%; p = 0.320), or <32 weeks (2.3% vs. 2.4%; p = 0.973). Nifedipine reduced spontaneous preterm delivery <37 weeks (p = 0.015) in the multiparous women by stratified analysis for parity. SECONDARY OUTCOMES between the groups did not differ except for a higher percentage of maternal side-effects in the nifedipine group (31.8%) vs. placebo (11.9%) (p < 0.05). Subgroup analysis showed a borderline (p = 0.047) lower percentage of spontaneous preterm delivery in women with a ultrasonographic cervical length of <20 mm in the nifedipine group. CONCLUSIONS: Prophylactic nifedipine in asymptomatic women at high risk for preterm delivery had a positive effect on the rate of spontaneous preterm delivery <37 weeks in multiparous women.

Early invasive diagnostic techniques in pregnant women who are infected with the HIV: a multicenter case series.

OBJECTIVE: Studies that mostly were conducted before the widespread use of combination antiretroviral treatments have reported that antenatal invasive procedures markedly increase the risk of human immunodeficiency virus vertical transmission. We aimed to evaluate the vertical transmission rate and other maternal and neonatal complications among women who were infected with human immunodeficiency virus who underwent antenatal invasive procedures during the second trimester of pregnancy and who were delivered after the advent of antiretroviral regimens. STUDY DESIGN: We conducted a multicenter case series of women who were infected with human immunodeficiency virus who underwent amniocentesis or chorionic villus sampling or cordocentesis during the second trimester of pregnancy and who were delivered after January 1, 1997. RESULTS: Sixty-three of 775 recruited women (8.1%) had performed early invasive diagnostic techniques . This rate has improved progressively from 4% in 1997 to 14%. Two of 60 viable infants (3.3%; 95% CI, 0.6%-10.1%) were infected with the human immunodeficiency virus. This rate did not differ significantly from the transmission rate that was observed in women who did not undergo antenatal invasive techniques (1.7%; P = .30). CONCLUSION: The current risk of human immunodeficiency virus vertical transmission that is associated with early invasive diagnostic techniques is lower than previously reported.