Alteraciones del bulbo olfatorio identificadas por resonancia magnética en una cohorte de pacientes con anosmia tras COVID-19 / Olfactory bulb abnormalities identified using magnetic resonance in a cohort of patients with anosmia after COVID-19

Resumen Dentro de los síntomas que presentaron los pacientes que cursaron COVID-19 se documentó una importante incidencia de anosmia, asociada muchas veces a alteraciones en el gusto, sin una base fisiopatológica concluyente. La resonancia magnética proporciona datos estructurales morfológicos sobre el nervio olfatorio, el bulbo olfatorio y las cortezas primarias y secundarias. En esta serie de pacientes con anosmia posterior a COVID-19 se identificaron alteraciones estructurales de los bulbos olfatorios principalmente con elevación de la señal en secuencias T2, y en menor medida aumento de su volumen. Dichas características fueron interpretadas en probable relación con edema e inflamación posterior a la infección viral, observando en ciertos casos, además, asimetría de los bulbos olfatorios.

Abstract Anosmia, a frequent symptom among patients affected by COVID-19 and often associated with alterations in taste, does not have a clear pathophysiological basis in this context. Magnetic resonance imaging enables the structural assessment of the olfactory nerve, olfactory bulb, and primary and secondary cortices. In this group of patients with post-COVID anosmia, were identified structural abnormalities at the level of the olfactory bulb mainly depicted as elevation of the signal in T2-weighted sequences, and to a lesser extent as an increase in their volume. These characteristics were interpreted in probable relation to edema and inflammation after the viral infection, showing in certain cases asymmetry of the olfactory bulbs.

PH negative acute lymphoblastic leukemia in adolescents and young adults treated according a MRD adapted BFM ALL IC 2009 protocol: Argentine real-world data on 171 patients.

Intensified pediatric chemotherapy regimens to treat adolescents and young adults (AYA) patients with Philadelphia negative acute lymphoblastic leukemia (ALL) have been associated with better outcomes. The local BFM 2009-based scheme complements the risk stratification assessing the measurable residual disease (MRD) along the induction phase with increasing levels of sensitivity. The present retrospective multicenter analysis included 171 AYA (15-40 years) patients treated accordingly between 2013 and 2019. Ninety-one percent obtained morphological complete remission, 67% a negative (<0.1%) MRD at day 33 (TP1), and 78% a negative (<0.01%) MRD at day 78 (TP2). The overall survival (OS) and the event-free survival (EFS) at 2 years were 62%±4.1 and 55%±4.1, respectively. The OS and EFS were significant better for prednisone responders, who achieved <10% BM blast at day 15, a negative MRD at TP1 or at TP2, and for low-risk patients. Age ≤30 years and WBC <30×109/L, particularly among B-phenotype, were also associated with longer OS. In the multivariable analyses, TP1 MRD positive (OS HR 2.8, 95% CI 1.4-5.7, p=0.004; EFS HR 3.0, 95% CI 1.6-5.7, p=0.001) and at TP2 (OS HR 2.6, 95% CI 1.3-5.3, p=0.012; EFS HR 2.6, 95% CI 1.3-5.1, p=0.006) were independently associated with earlier events. Age >30 years was also associated with a shorter survival (HR 3.1, 95% CI 1.3-7.5, p=0.014). Therefore, those 68 patients ≤30 years with TP1/TP2 negative MRD depicted a longer OS (2 years 85%±4.8). Based on our real-world data, the pediatric-based scheme is feasible in Argentina associated with better outcomes for younger AYA patients who achieved negative MRD at day 33 and 78.

Coronavirus: experiencia en el departamento de imágenes de un hospital universitario / Coronavirus: Experience in the radiology department of an university hospital

Resumen Objetivo: Dar a conocer la experiencia en nuestro departamento de imágenes y presentar los hallazgos de radiografía (Rx) y tomografía computada (TC) que hemos observado en nuestra serie de casos con diagnóstico confirmado de COVID-19. Método: Estudio retrospectivo analítico de los hallazgos de Rx y TC en una serie de pacientes que asistieron al servicio de urgencias por sospecha de COVID-19 en los hospitales universitarios dependientes de nuestra institución en el periodo comprendido entre el 1 de marzo y el 31 de mayo de 2020. Resultados: En el período de estudio se detectaron 127 casos de COVID-19 positivos en nuestra institución. A 57 (45%) de ellos se les realizó Rx. En 46 (80%) de ellas no mostraron hallazgos patológicos. En 8 (14%) pacientes se observaron opacidades parcheadas en vidrio esmerilado y en 3 (5%) en asociación con consolidaciones. La distribución fue predominantemente bilateral y en los lóbulos inferiores. A 11 pacientes se les realizó TC de tórax y 9 (81%) manifestaron infiltrados en vidrio esmerilado, mostrando preferencia por las áreas periféricas y los lóbulos superiores, asociándose a consolidaciones en 4 (36%) casos. Un paciente (9%) presentó patrón en empedrado y otros 2 mostraron opacidades (18%) redondeadas en vidrio esmerilado. Dos pacientes (18%) no tuvieron hallazgos patológicos. Como hallazgos atípicos, se evidenció derrame pleural en 2 pacientes (18%) y neumotórax en uno (9%) en uno de ellos. Conclusiones: Nuestra experiencia demostró como características frecuentes la presencia de opacidades parcheadas en vidrio esmerilado y consolidaciones parcheados de distribución predominantemente en los lóbulos inferiores.

Abstract Objective: To show the experience in our radiology department at X-ray and computed tomography (CT) imaging findings in patients with confirmed COVID-19. Method: Retrospective analytical study of the radiological findings on X-ray and CT on a series of patients who attended the emergency department on suspicion of COVID-19 at university hospitals dependent of our institution in the period between March 1 and May 31, 2020. Results: During the study period, 127 cases of COVID-19 were detected in our institution. X-rays were performed in 57 (45%) of them, 46 (80%) of which did not show pathological findings. In total, 8 (14%)manifested as patchy ground glass opacities, and 3 (5%), in association with consolidations. The distribution was predominantly bilateral and in the lower lobes. Eleven patients underwent chest CT, 9 (81%) of these showed ground glass opacities, showing a preference for peripheral areas and upper lobes, associated with consolidations in 4 (36%) of them. One patient (9%) presented crazy paving and 2 rounded (18%) ground glass opacities. Two patients (18%) showed no pathological findings. As atypical findings, pleural effusion was evident in two (18%) patients, and pneumothorax, in one (9%). Conclusions: Our experience demonstrated the presence of patchy ground glass opacities and patchy consolidative opacities predominantly in the lower lobes as frequent features.

No dejemos morir al hueso: interiorizándonos con los procesos óseos avasculares / Do not let the Bone Die: Interiorizing with the avascular Bone Processes

Resumen El objetivo de este artículo es realizar una revisión de las localizaciones, causas y hallazgos radiológicos específicos de los procesos avasculares óseos. Se define como isquemia ósea a las alteraciones ocasionadas por déficit de irrigación, llevando a la destrucción del hueso. Existen diferencias entre necrosis isquémica e infarto óseo, en base al sitio óseo de afectación. La etiología traumática es la más frecuente y suele ser unilateral. Los sitios de presentación más frecuentes son: cabeza femoral y humeral, rodilla y semilunar. La resonancia magnética (RM) es considerada la modalidad de imagen más sensible y específica, tanto para el diagnóstico temprano como estadificación y control. El conocimiento de las causas, características radiológicas y sus diferentes fases evitan el diagnóstico erróneo de otras etiologías, como las primarias o infecciosas, facilitando un correcto algoritmo terapéutico.

Abstract The aim of this article is to review the locations, causes and specific radiological findings of avascular bone processes. Bone ischemia is defined as the alterations caused by irrigation deficit, leading into the bone destruction. However, there are differences between ischemic necrosis and bone infarction, based on the bone site of involvement. The most frequent etiology is traumatic and is usually unilateral. The most frequent sites of presentation are: femoral and humeral head, knee, and lunate. Magnetic resonance imaging (MRI) is considered the most sensitive and specific imaging modality for early diagnosis, staging and control. The knowledge of the causes, radiological findings and their different phases avoid the erroneous diagnosis of other lesions, such as primary or infectious, facilitating a correct therapeutic algorithm.

Long-term follow-up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according to JAK2/CALR/MPL mutational status.

BACKGROUND: Anagrelide represents a treatment option for essential thrombocythemia, although its place in therapy remains controversial. AIM: To assess the impact of mutational status in response rates and development of adverse events during long-term use of anagrelide. METHODS: We retrospectively evaluated 67 patients with essential thrombocythemia treated with anagrelide during 68 (4-176) months. RESULTS: Mutational frequencies were 46.3%, 28.3%, and 1.5% for JAK2V617F, CALR and MPL mutations. Anagrelide yielded a high rate of hematologic responses, which were complete in 49.25% and partial in 46.25%, without differences among molecular subsets. The rate of thrombosis during treatment was one per 100 patient-years, without excess bleeding. Anemia was the major adverse event, 30.3% at 5-yr follow-up, being more frequent in CALR(+) (P < 0.05). Myelofibrotic transformation developed in 14.9% (12.9%, 21%, and 12.5% in JAK2V617F(+), CALR(+), and triple-negative patients, respectively, P = NS) and those treated >60 months were at higher risk, OR (95% CI) 9.32 (1.1-78.5), P < 0.01, indicating the need for bone marrow monitoring during prolonged treatment. CONCLUSION: Although CALR(+) patients were at higher risk of developing anemia, anagrelide proved effective among all molecular subsets, indicating that mutational status does not seem to represent a major determinant of choice of cytoreductive treatment among essential thrombocythemia therapies.

Gonadal steroids modulate Fas-induced apoptosis of lactotropes and somatotropes.

We have previously reported that Fas activation induces apoptosis of anterior pituitary cells from rats at proestrus but not at diestrus and in an estrogen-dependent manner. In this study, we evaluated the effect of Fas activation on apoptosis of lactotropes and somatotropes during the estrous cycle and explored the action of gonadal steroids on Fas-induced apoptosis. Also, we studied whether changes in Fas expression are involved in the apoptotic response of anterior pituitary cells. Fas activation increased the percentage of TUNEL-positive lactotropes and somatotropes at proestrus but not at diestrus. FasL triggered apoptosis of somatotropes only when cells from ovariectomized rats were cultured in the presence of 17 ß-estradiol (E2). Progesterone (P4) blocked the apoptotic action of the Fas/FasL system in lactotropes and somatotropes incubated with E2. Both E2 and P4 increased the percentage of cells expressing Fas at the cell membrane. Our results show that Fas activation induces apoptosis of lactotropes and somatotropes at proestrus but not at diestrus. Gonadal steroids may be involved in the apoptotic response of lactotropes and somatotropes, suggesting that Fas activation is implicated in the renewal of these pituitary subpopulations during the estrous cycle. The effect of gonadal steroids on Fas expression may be only partially involved in regulation of the Fas/FasL apoptotic pathway in the anterior pituitary gland.

Granulomatosis de Wegener y tuberculosis: Una mala combinación / Wegener's granulomatosis and tuberculosis: A bad combination

La enfermedad de Wegener es una vasculitis de pequeños y medianos vasos asociada a anticuerpos anticitoplasma del neutrófilo (ANCA). Dentro de los órganos blancos, el pulmón se encuentra comprometido en el 85% de los casos. Numerosas entidades deben ser consideradas en el diagnóstico diferencial, entre ellas, la tuberculosis pulmonar. Presentamos el caso de un hombre de 54 años de edad, con diagnóstico en el año 1996 de enfermedad de Wegener, que comienza en agosto de 2007 con expectoración hemoptoica, disnea de esfuerzo progresiva y esputo con baciloscopia BAAR (+), por lo que inicia tratamiento antituberculoso. La baciloscopia no se constata en dos lavados broncoalveolares contemporáneos. Evoluciona con deterioro de la función renal, púrpura palpable y anticuerpos anticitoplasma del neutrófilo patrón citoplasmático (ANCA-c) positivo. Se interpreta reactivación de su enfermedad de base. Inicia tratamiento inmunosupresor y hemodiálisis y suspende tratamiento antituberculoso. Un mes después del alta se reinterna con cuadro similar al previo, con esputo seriado positivo para BAAR.

Wegener's disease is a vasculitis of small and medium-sized vessels associated with anti-neutrophil cytoplasm antibodies (ANCA). Within their target organs the lungs are involved in 85% of cases. Many entities are part of the differential diagnosis, including pulmonary tuberculosis. We present the case of a 54 years old man, diagnosed as Wegener's disease in 1996 which begins in August 2007 with cough, hemoptysis, progressive dyspnea on effort and serial sputum positive for AFB and then starts TB treatment. Subsequent bronchoalveolar fluids resulted negative for AFB. The patient evolved with impaired renal function, palpable purpura and positive anti-neutrophil cytoplasm antibodies cytoplasmic pattern (c-ANCA), interpreted as Wegener's disease relapse. He started hemodialysis and immunosuppressive therapy and tuberculosis treatment was stopped. One month after discharge was readmitted with a similar picture with serial sputum positive for AFB.

[Wegener's granulomatosis and tuberculosis. A bad combination]. / Granulomatosis de Wegener y tuberculosis. Una mala combinación.

Wegener's disease is a vasculitis of small and medium-sized vessels associated with anti-neutrophil cytoplasm antibodies (ANCA). Within their target organs the lungs are involved in 85% of cases. Many entities are part of the differential diagnosis, including pulmonary tuberculosis. We present the case of a 54 years old man, diagnosed as Wegener's disease in 1996 which begins in August 2007 with cough, hemoptysis, progressive dyspnea on effort and serial sputum positive for AFB and then starts TB treatment. Subsequent bronchoalveolar fluids resulted negative for AFB. The patient evolved with impaired renal function, palpable purpura and positive anti-neutrophil cytoplasm antibodies cytoplasmic pattern (c-ANCA), interpreted as Wegener's disease relapse. He started hemodialysis and immunosuppressive therapy and tuberculosis treatment was stopped. One month after discharge was readmitted with a similar picture with serial sputum positive for AFB.

Ribosome binding site recognition using neural networks

Pattern recognition is an important process for gene localization in genomes. The ribosome binding sites are signals that can help in the identification of a gene. It is difficult to find these signals in the genome through conventional methods because they are highly degenerated. Artificial Neural Networks is the approach used in this work to address this problem.

Reaçoes de imunofluorescência indireta para toxoplasmose em pacientes com síndrome da imunodeficiência adquirida / Immunofluorescence tests for toxoplasmosis in patients with AIDS

Foram processadas 1.050 amostras de soro e/ou líquido cefalorraquidiano (LCR) de 450 pacientes do Estado de Säo Paulo com pesquisa positiva para anticorpos anti-HIV. Foi estudada a prevalência de anticorpos anti-Toxoplasma gondii através da reaçäo de imunofluorescência indireta nesses pacientes. Foram dosados anticorpos anti-T. gondii das classes Igtotal e IgM específico. Os resultados revelaram positividade par Igtotal nas amostras de soro e LCR em 69,1% e 47,3%, respectivamente. Em relaçäo às imunoglobulinas IgM, a sorologia mostrou-se positiva em 2,8% das amostras. Observou-se ainda elevada reatividade para Igtotal em amostras de LCR (61,2%) em pacientes com quadro clínico compatível com toxoplasmose. A concomitância de positividade em amostras de soro e LCR mostrou-se crescente, quanto mais avançada a fase clínica em que os pacientes com SIDA (AIDS) se encontravam. Em pacientes do grupo IV (ARC) da SIDA, quando os títulos de Igtotal no soro sanguíneo foram>/1.024, a concomitância de positividade no LCR foi de 80%..

Enteroparasitoses em pacientes acometidos pela síndrome de imunodeficiência adquirida (AIDS/SIDA) / Intestinal parasitic infections among patients with acquired immunodeficiency syndrome (AIDS)

No período compreendido entre fevereiro de 1984 e abril de 1987, examinaram-se, na Seção de Enteroparasitoses do Instituto Adolfo Lutz, 771 amostras de fezes de pacientes atendidos pelo Programa de Controle e Prevenção da AIDS, da Secretaria de Estado da Saúde de São Paulo. Do total, 483 pacientes estavam acometidos por AIDS e os demais 288 pertenciam a grupos de risco para infecção por HIV. Examinaram-se, também, no mesmo período, as fezes de 432 indivíduos atendidos por Unidades Sanitárias mantidas pela rede estadual de atenção primária à saúde, que, por sorteio, constituíram grupo controle. Os resultados indicaram maior frequência de parasitismo por Entamoeba histolytica e Isospora belli entre os pacientes aidéticos e os pertencentes a grupos de risco para infecção por HIV, além de índices mais elevados de infecção por Strogyloides stercoralis entre os aidéticos, quando comparados aos demais grupos. Revelou-se, ainda, infecção por Crytosporidium sp. em 12,1% dos aidéticos e 2,5% dos componentes de grupos de risco (AU).