Impacto de la Terapia de Alto Flujo de Oxigeno (TAFO) en un Hospital Pediátrico de la Provincia de Buenos Aires / Impact of High Flow Oxygen Therapy (TAFO) in a Pediatric Hospital of the Province of Buenos Aires

Introducción: Las infecciones respiratorias agudas bajas (IRAB), representan la causa más frecuente de consulta e internación en los meses de invierno. La insuficiencia respiratoria aguda es la complicación que motiva la internación de los pacientes y la necesidad de Unidad Terapia Intensiva (UTI).El objetivo del trabajo fue describir los resultados de la implementación de la Terapia de Alto Flujo (TAFO) en pacientes con IRAB grave internados en Terapia Intermedia Métodos: Estudio prospectivo y descriptivo que incluyó pacientes de 1 a 36 meses internados en Terapia Intermedia en el Hospital Sor María Ludovica de la ciudad de La Plata, desde junio de 2018 a septiembre de 2019. Se ingresaron a TAFO pacientes sin respuesta al tratamiento con oxígeno a bajo flujo. El ingreso a UTI se consideró fracaso de la TAFO Resultados: De 760 pacientes internados con IRAB, 91(11,9%) ingresaron a TAFO de los cuales 59 (64,8 %) tuvieron respuesta favorable con disminución de la frecuencia respiratoria (FR), frecuencia cardiaca (FC) y mejoría de la mecánica respiratoria; el resto (35,2%) pasó a UTI por fracaso terapéutico. Presentaron complicaciones a la TAFO el 5,5% de los pacientes Conclusión: La TAFO fue una terapéutica segura, de fácil utilización que, a través de un aporte de oxígeno conocido, permitió la corrección de la hipoxemia, logrando la disminución de la FR, FC y mejoría de la mecánica respiratoria, dándole mayor comodidad al paciente durante su enfermedad

Introduction: Respiratory infections remain the major cause of outpatient consultation and hospital admissions during the winter season. Lower respiratory illness may cause severe acute respiratory insufficiency and hypoxemic respiratory failure, thus determining the need for hospitalization and eventual intensive care (ICU). The purpose of this paper is to describe the results of High Flow Oxygen Therapy (HFOT) implementation for patients with acute lower respiratory infections (ALRI) admitted to intermediate therapy unit. Methods: Prospective and descriptive study which included patients from age 1 to 36 months, hospitalized at intermediate therapy care unit at "Sor María Ludovica", Hospital, in La Plata, from June, 2018 to September, 2019. Patients who did not show any improvement to low flow oxygen therapy were the subjects of this study. Further submission to ICU was considered as HFOT failure Results: From 760 patients hospitalized with ALRI, 91 (11.9%) were admitted to TAFO. Fifty nine, (64.8%) had a favorable response with decreased respiratory and heart frequency rate, and an improvement of the work of breathing. The rest (35.1%) went to ICU due to therapeutic failure. Five point five percent of patients presented complications to TAFO. Conclusion: HFOT was a safe, easy to implement therapy treatment which improved the hypoxemic respiratory failure. This therapy reduced the respiratory and heart rate, and yielded a better and lower respiratory work, making patients more comfortable during illness

Association between Degree of Anaplasia and Degree of Inflammation with the Expression of COX-2 in Feline Injection Site Sarcomas.

Feline injection site sarcomas (FISSs) are mesenchymal neoplasms that develop at the sites of delivery of vaccines or other injectable products. Vaccine adjuvants can trigger an intense and persistent inflammatory response that may lead to neoplastic transformation. The proinflammatory role of cyclo-oxygenase (COX)-2 is well known and its overexpression has prognostic value in multiple neoplastic processes. One hundred and seventeen FISSs were evaluated for the degree of inflammation and anaplasia. Immunohistochemistry was used to determine the expression of COX-2 in these sarcomas. There was a significant association between the degree of inflammation and the expression of COX-2 by neoplastic cells. COX-2 expression was lower in tumours with higher degrees of anaplasia. These findings may be useful in predicting the sensitivity of FISSs to treatment with COX-2 inhibitors. The potential therapeutic use of such agents could then be restricted to tumours with lower degrees of anaplasia.

STANDING, a four-step bedside algorithm for differential diagnosis of acute vertigo in the Emergency Department.

Vertigo is generally due to a benign disorder, but it is the most common symptom associated with misdiagnosis of stroke. In this pilot study, we preliminarily assessed the diagnostic performance of a structured bedside algorithm to differentiate central from non-central acute vertigo (AV). Adult patients presenting to a single Emergency Department with vertigo were evaluated with STANDING (SponTAneous Nystagmus, Direction, head Impulse test, standiNG) by one of five trained emergency physicians or evaluated ordinarily by the rest of the medical staff (control group). The gold standard was a complete audiologic evaluation by a clinicians who are experts in assessing dizzy patients and neuroimaging. Reliability, sensibility and specificity of STANDING were calculated. Moreover, to evaluate the potential clinical impact of STANDING, neuroimaging and hospitalisation rates were compared with control group. A total of 292 patients were included, and 48 (16.4%) had a diagnosis of central AV. Ninety-eight (33.4%) patients were evaluated with STANDING. The test had good interobserver agreement (k = 0.76), with very high sensitivity (100%, 95%CI 72.3-100%) and specificity (94.3%, 95%CI 90.7-94.3%). Furthermore, hospitalisation and neuroimaging test rates were lower in the STANDING than in the control group (27.6% vs. 50.5% and 31.6% vs. 71.1%, respectively). In conclusion, STANDING seems to be a promising simple structured bedside algorithm that in this preliminary study identified central AV with a very high sensitivity, and was associated with significant reduction of neuroimaging and hospitalisation rates.

Lack of association between MDM2 SNP309 and TP53 Arg72Pro polymorphisms with clinical outcomes in myelodysplastic syndrome.

MDM2/p53 pathway plays an important role in the control of apoptotic and proliferation mechanisms, and alterations in this pathway have been described in myelodysplastic syndromes (MDS). We investigated the frequency of MDM2 SNP309, TP53 Arg72Pro polymorphisms in de novo MDS and the association of these polymorphisms with clinical characteristics. Our results showed that the frequencies of genotypes for MDM2 SNP309 and TP53 Arg72Pro did not differ between MDS and healthy controls and that these polymorphisms were not associated with clinical and laboratory parameters, disease progression and overall survival, suggesting that MDM2 and TP53 polymorphisms are not involved in risk for MDS, or in the clinical and laboratory characteristics of the disease.

Comparison of two prognostic models for acute pulmonary embolism: clinical vs. right ventricular dysfunction-guided approach.

BACKGROUND: Recently, some prognostic models for acute pulmonary embolism (PE) have been proposed. We investigated whether the Pulmonary Embolism Severity Index (PESI) and the European Society of Cardiology (ESC) prognostic approaches result in different prognoses. METHODS: Consecutive adult patients with acute PE were included. According to the ESC guidelines, high-risk patients were identified by the presence of shock/hypotension, intermediate-risk patients by elevated troponin I or right ventricular dysfunction as assessed by echocardiography, and low-risk patients by the absence of any of the above. In the PESI model, 11 clinical variables, easily accessible at the bedside, were used to generate three risk classes. The main outcomes were all-cause and PE-related in-hospital mortality. RESULTS: Forty-one patients (8%, 95% confidence interval [CI] 5.8-10.8) of 510 died. According to the ESC model, 40% were at low risk of short-term mortality, 54% at intermediate risk, and 6% at high risk. The distribution according to the PESI model was 31% (P < 0.05 vs. ESC), 49% and 20% (P < 0.05 vs. ESC), respectively. Mortality increased through the risk classes (P < 0.01), without significant differences between the models. The ESC model identified with higher accuracy than the PESI model both high-risk and low-risk patients (P < 0.05 for both). When patients with shock/hypotension were excluded, the PESI model stratified patients into classes with increasing PE-related mortality (0.7%, 4.3%, and 11.6%, P < 0.05). Troponin I and right ventricular dysfunction added incremental prognostic value to the PESI model, particularly in normotensive patients at intermediate risk. CONCLUSIONS: The ESC model showed higher accuracy than the PESI model in identifying high-risk and low-risk patients. In normotensive patients, the PESI model could guide clinical management as well as troponin I and echocardiography testing.

Improved outcome in young adults with de novo acute myeloid leukemia in first remission, undergoing an allogeneic bone marrow transplant.

We assessed the outcome of 170 patients with AML in first complete remission, aged 1-47 years (median 29), who had undergone an allogeneic BMT before or after 1990 (n=80 and n=90, respectively); all patients were prepared with cyclophosphamide and TBI; the median follow-up for surviving patients was 13 years. The donor was an HLA-identical sibling in 164 patients. Transplant-related mortality (TRM) was 30% before and 7% after 1990 (P<0.001); relapse-related death (RRD) was 26 and 11% (P=0.002); and actuarial 10-year survival was 42 and 79% (P<0.00001). Patients transplanted after 1990 were older, had a shorter interval diagnosis-BMT, had less FAB-M3 cases, received a higher dose of TBI, a higher marrow cell dose and combined (cyclosporine+methotrexate) GVHD prophylaxis. Patients relapsing after transplant had an actuarial survival of 0 vs 31% if grafted before or after 1990 (P=0.01), and their median follow-up exceeds 10 years. In conclusion, the overall survival of first remission AML undergoing an allogeneic BMT has almost doubled in the past two decades, despite older age and fewer M3 cases. Improvement has come not only from changes in transplant procedures, but also from effective rescue of patients relapsing after transplant.

Immune system pathogenesis is prevented by the neutralization of the systemic trans-sialidase from Trypanosoma cruzi during severe infections.

During the acute phase of Trypanosoma cruzi infection, strong haematological and immune system alterations are observed. The parasite expresses trans-sialidase, a virulence factor responsible for the sialylation of its surface glycoconjugates. This enzyme is also shed to the bloodstream where it is associated with immune system alterations triggered during the infection. During experimental and human infections, the host elicits antibodies able to neutralize the enzyme activity that would be responsible for restricting systemic trans-sialidase to the early steps of the infection, when major immune alterations are induced. The actual relevance of these antibodies was tested by passive transference of monoclonal neutralizing antibodies in acute infection models displaying extreme sensitivity to the infection. Mice were inoculated with virulent parasite strains that induce high parasitaemia, early mortality and strong immune tissue abnormalities. The trans-sialidase-neutralizing antibodies were able to preserve B cell areas both in ganglia and spleen as well as the thymus architecture even in these extreme models. Although no differences between control and treated mice regarding animal survival were found, a major role for the humoral response in controlling the damage of the immune system induced by a systemically distributed virulence factor was defined in an infection with a eukaryotic pathogen.

Feline immunodeficiency virus infection: a comparative study of different diagnostic techniques

Avaliou-se a técnica de imunofluorescência indireta (IFA) na detecção de anticorpos contra o vírus da imunodeficiência felina (FIV) numa pesquisa epidemiológica do FIV na Argentina. A IFA foi modificada e comparada com duas outras técnicas imunológicas: western blot (WB) e imunocromatografia em camadas (SI) com kit comercial e também com reação em cadeia de polimerase (PCR) para detecção do DNA proviral. A IFA mostrou ser um teste com alta sensibilidade e especificidade e poderá ser empregada como ferramenta útil em estudos epidemiológicos. A baixa porcentagem de reatividade não específica pode ser esclarecida com testes mais avançados ou usando métodos alternativos.

Evaluación de la calidad y la satisfacción de la recuparación posanestésica de los pacientes operados en el Hospital de Clínicas / Evaluation of quality and satisfaction of postanesthetic recovery of the patients operated in the Hospital de Clínicas

La evaluación de la calidad asistencial a través de resultados (morbilidad y mortalidad) deja de lado la experiencia subjetiva del paciente. En este estudio se analizó el aspecto subjetivo de la recuperación anestésica mediante una escala visual análoga de satisfacción (EVA) y un cuestionario dirigido a evaluar la calidad de la asistencia anestesiológica. Se entrevistaron, a las 24 horas del alta de la sala de recuperación, 166 pacientes operados de coordinación. A cada pregunta se le asignó un valor numérico y se construyó un score global de calidad (QoR39). Las preguntas se agruparon en función a cinco aspectos de la recuperación: confort, emociones, independencia física, apoyo psicológico y dolor. El valor promedio del QoR39 fue de 175,33±ll,3 (89,9 por ciento del puntaje máximo). Los aspectos que mostraron valores más altos de puntuación fueron el apoyo psicológico y el dolor; y los más bajos fueron la independencia física y el confort. Las emociones obtuvieron un valor intermedio. Existen diferencias significativas entre los promedios del QoR39 en relación al tipo de anestesia, complicaciones en el área de recuperación y estado físico (ASA 3). El promedio del valor de la escala de satisfacción fue de 7,45±1,87; un 30 por ciento de la población señala valores menores a 7, un 38 por ciento marcó valores entre 7 y 8,5 y un 30 por ciento entre 9 y 10. Se identificó una relación directa entre los valores de EVA y de QoR39 con r=0,73 (p < 0,007). La experiencia del paciente evaluada a través de la satisfacción global (EVA) y de la calidad de recuperación (QoR39) constituye una medida cuantitativa de la calidad de recuperación posoperatoria y nos permite realizar un seguimiento del proceso de atención, identificando los aspectos que más se afectan por la cirugía y la anestesia en la población hospitalaria.

Fludarabine, ARA-C, idarubicin and G-CSF (FLAG-Ida), high dose ARA-C and early stem cell transplant. A feasable and effective therapeutic strategy for de novo AML patients.

Forty-three consecutive patients with de novo and untreated non M3 AML aged 60 or less entered the study. The mean age of patients was 50 (range 15-60). The induction regimen (FLAG-Ida) included fludarabine (30 mg/sqm), Ara-C (2 g/sqm) on days 1-5, and idarubicin (10 mg/sqm) on days 1, 3, 5. G-CSF (300 mcg/day) was administered s.c. 12 hours before starting fludarabine and was continued for five days. HDT with stem cell rescue was planned for all patients in first CR after one course of high dose Ara-C (HDAC) consolidation and in good clinical conditions. Forty-two (98%) patients were evaluable for response. One patient died during induction (2%). CR was achieved in 35 patients (82%). Twenty-three patients, 66% of those achieving CR, underwent autologous (N = 17) or allogeneic (N = 6) transplantation. With a median follow up of 24 months, the average median duration of CR is 17 months (range 3-66) and the median survival is 20 months (range 1-83). Overall the 5 year projected disease free survival (DFS) and overall survival (OS) were 37% and 43%, respectively. Among patients who underwent stem cell transplantation DFS and OS were 53% and 69%, respectively. The median time to PMN recovery (> 0.5 x 10(9)/l) was 17 days (range 10-28) and 50 x 10(9)/l platelets were reached at a median of 17 days (12-38). In conclusion FLAG-Ida regimen is effective, low toxic and improves feasibility of stem cell transplant.

1,2,5-Oxadiazole N-oxide derivatives as potential anti-cancer agents: synthesis and biological evaluation. Part IV.

Several new 1,2,5-oxadiazole N-oxide derivatives and some deoxygenated analogues were synthesized to be tested as potential selective hypoxic cell cytotoxins. Compounds prepared were designed in order to gain insight into the mechanism of action of this kind of cytotoxin. Compounds were tested in oxia and hypoxia and they proved to be non-selective. 3-Cyano-N(2)-oxide-4-phenyl-1,2,5-oxadiazole showed the best cytotoxic activity in oxia. The cytotoxicity observed for these derivatives could be explained in terms of the electronic characteristics of the 1,2,5-oxadiazole substituents. Electrochemical and ESR studies were performed on the more cytotoxic derivative.

Antibody maturation in Trypanosoma cruzi-infected rats.

The study of antibody avidity changes during infection has improved the understanding of the pathologic processes involved in several infectious diseases. In some infections, like toxoplasmosis, this information is being used for diagnostic purposes. Results of the evolution of antibody avidity for different specific antigens in Trypanosome cruzi-infected rats are presented. A Western blotting technique, combined with avidity analysis to identify antigens that elicit high-avidity antibodies, is suggested. In this system, antibodies showed high avidity values only during the chronic phase of infection and only in relation to antibodies against 21-, 33-, 41-, 42-, 56-, 58-, 66-, and 72-kDa antigens. Finally, a 97-kDa T. cruzi antigen, which was recognized by high-avidity antibodies and occurred in noninfected rats, was identified. These results allow us to evaluate the different antigens in chagasic infection. Our results show that with the correct choice of antigen it is possible to detect differences in maturation of antibodies and to discriminate, in an experimental model, between recent (acute) and chronic infections.

Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as potential hypoxic cytotoxins and DNA-binders.

Several new 1,2,5-oxadiazole N-oxide derivatives were synthesized to be tested both as potential selective hypoxic cell cytotoxins and as DNA-binding agents. The compounds prepared included bis(1,2,5-oxadiazole N-oxide) derivatives and oxadiazole rings linked to naphthyl residues. The compounds were tested for their cytotoxicity in oxia and hypoxia and they proved to be non-selective and less active than the parent compounds 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide (3) and 3-chloromethyl-4-phenyl-1,2,5-oxadiazole N2-oxide (4). The DNA-affinity assays showed that the compounds tested have poor affinity for this biomolecule.

Synthesis and antitrypanosomal evaluation of E-isomers of 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives. structure-activity relationships.

Several novel semicarbazone derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde and semicarbazides bearing a spermidine-mimetic moiety. All derivatives presented the E-configuration, as determined by NMR-NOE experiments. These compounds were tested in vitro as potential antitrypanosomal agents, and some of them, together with the parent compounds, 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives, were also evaluated in vivo using infected mice. Structure-activity relationship studies were carried out using voltammetric response and lipophilic-hydrophilic balance as parameters. Two of the compounds (1 and 3) displayed the highest in vivo activity. A correlation was found between lipophilic-hydrophilic properties and trypanocidal activity, high R(M) values being associated with low in vivo effects.

Alpha-interferon as induction and maintenance therapy in hairy cell leukemia: a long-term follow-up analysis.

Although in recent years the use of purine analogues has increased the percentage of long-term complete response the effect on overall survival of patients with hairy cell leukemia (HCL) is not yet clear. This study aimed to evaluate the long-term outcome (mean follow up of 92 months) of 64 patients receiving IFN as first-line therapy. IFN was well tolerated and effective. The overall response rate was 91% (PR 65%, CR 13%, GPR 13%). Forty-one patients (63%) received IFN 3 MU/ wk as maintenance therapy. The 10-yr projected survival rate of responding patients (CR and GPR 100%; PR 95%) and non-responders (SD, PD 80%) clearly shows that type of response does not affect survival. Patients receiving IFN maintenance had a statistically higher PFS than those who did not (p <0.01). This study shows that IFN is still one of the standard therapies for this disease, that achieving CR has no primary relevance for the control of the disease, and that good utilization of therapeutic resources may assure HCL patients a survival rate comparable to that of a normal, healthy population.

1,2,5-Oxadiazole N-oxide derivatives and related compounds as potential antitrypanosomal drugs: structure-activity relationships.

The syntheses of a new series of derivatives of 1,2,5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline di-N-oxide are described. In vitro antitrypanosomal activity of these compounds was tested against epimastigote forms of Trypanosoma cruzi. For the most effective drugs, derivatives IIIe and IIIf, the 50% inhibitory dose (ID50) was determined as well as their cytotoxicity against mammalian fibroblasts. Electrochemical studies and ESR spectroscopy show that the highest activities observed are associated with the facile monoelectronation of the N-oxide moiety. Lipophilic-hydrophilic balance of the compounds could also play an important role in their effectiveness as antichagasic drugs.

Five day intermittent vs seven day continuous 2-chlorodeoxyadenosine infusion for the treatment of hairy cell leukemia. A study by Italian Group for the Hairy Cell Leukemia.

The new purine-analogue 2-chlorodeoxyadenosine (2-CdA) has proved to induce an high CR rate and a long lasting disease free survival. In this study we compare the efficacy and toxicity of 2-CdA employed in two different schedules (A and B). Forty-one patients have been enrolled from 1994: 22 p. (group A) were treated with a single cycle of 2-CdA given as two hour i.v. infusion on 5 consecutive days (0.15 mg/kg/die); while 19 p. (group B) with continuous i.v. infusion for 7 consecutive days (0.10 mg/kg/die). Response criteria were those proposed by NCI. The Hairy Cell Index (HCI) was calculated using DBA44 MoAb. At three months, the responses in group A (19/22) were: 5 CR (26.3%), 6 GPR (31.5%), 5 PR and 3 NR.; in group B (17/19): 6 CR (35.3%), 3 GPR (17.6%), 4 PR and 4 NR. Overall response at six months was respectively 84.2% and 76.5%. At six months the responses were: in group A (18/22): 9 CR (50%), 4 GPR (22.2%), 3 PR, 2 NR; in group B (16/19): 4 CR (25%), 6 GPR (37.5%), 3 PR, 3 NR. Overall response at 6 months was respectively 88.8% (group A) and 81.2% (group B). The 5 day intermittent schedule appears efficient, well tolerated and suitable for out-patient treatment. DBA44 MoAb appears useful to better define the HCI and to distinguish CR from GPR.