Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey.

OBJECTIVES: We evaluated azacitidine (Vidaza(®)) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. METHODS: This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010-2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. RESULTS: The median age of patients was 74·7 (range: 43·9-87·8) years; 69·4% had MDS, 26·5% had primary or secondary AML, and 4·1% had CMML. Treatment-related TEAEs, grade 3-4 TEAEs, and TESAEs were reported in 67·3%, 28·6%, and 18·4% of patients, respectively. During 1YOP, patients received a median of 7 (1-12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (n = 29), 41·4% had CR, PR, or HI, 41·4% had SD, and 17·2% had TF. Among AML patients (n = 9), 44·4% had CR or PR, 33·3% had SD, and 22·2% had TF. TI was observed in 14/32 (43·8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326-555) days; 1-year OS estimate was 0·571 (0·422-0·696). CONCLUSIONS: Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.

Subclavian artery resection and reconstruction for thoracic inlet neoplasms.

BACKGROUND: To update the long-term outcomes after subclavian artery (SA) resection and reconstruction during surgery for thoracic inlet (TI) cancer through the anterior transclavicular approach. METHODS: Between 1985 and 2014, 85 patients (60 men and 25 women; mean age, 52 years) underwent en bloc resection of thoracic-inlet non-small cell lung cancer (NSCLC) (n=69), sarcoma (n=11), breast carcinoma (n=3) or thyroid carcinoma (n=2) involving the SA. L-shaped transclavicular cervicothoracotomy was performed, with posterolateral thoracotomy in 18 patients or a posterior midline approach in 15 patients. Resection extended to the chest wall (>2 ribs, n=60), lung (n=76), and spine (n=15). Revascularization was by end-to-end anastomosis (n=48), polytetrafluoroethylene (PTFE) graft interposition (n=28), subclavian-to-common carotid artery transposition (n=8), or grafting of the autologous superficial femoral artery in an anterolateral thigh free flap (n=1). Complete R0 resection was achieved in 75 patients and microscopic R1 resection in 10 patients. Postoperative radiation therapy was given to 51 patients. RESULTS: There were no cases of postoperative death, neurological sequelae, graft infection or occlusion, or limb ischemia. Postoperative morbidity consisted of pneumonia (n=16), phrenic nerve palsy (n=2), recurrent nerve palsy (n=4), bleeding (n=4), acute pulmonary embolism (n=1), cerebrospinal fluid leakage (n=1), chylothorax (n=1), and wound infection (n=2). Five-year survival and disease-free survival rates were 32% and 22%, respectively. Long-term survival was not observed after R1 resection. CONCLUSIONS: Subclavian arteries invaded by TI malignancies can be safely resected and reconstructed through the anterior transclavicular approach, with good long-term survival provided complete R0 resection is achieved.

¿Cuántas víctimas se necesitan para definir un desastre? / How many victims are needed to define a disaster?

Objetivo. Describir una situación de atención de víctimas múltiples. Analizar las características particulares del síndrome de inhalación de humo (SIH). Material y Métodos. Se evaluaron 5 pacientes (pts), ingresados al Servicio de Emergencias del HRRG en Noviembre del 2006, de los cuales tres ingresaron al Servicio de Terapia Intensiva (STI), único en la zona norte de la Provincia de Tierra del Fuego. La capacidad instalada del Hospital es de 5 camas de Terapia Intensiva con 5 respiradores microprocesador y con un ingreso anual de 300 pts con un índice de ocupación de camas de 5.4 pts/día. Los motivos de ingreso al STI fueron: Síndrome de Inhalación de Humo (SIH) e Insuficiencia Respiratoria Aguda. Se dividió a las Lesiones de la Inhalación de Humo (LIH) en: Lesión Térmica de la Vía Aérea (LTVA), Asfixia (A) y Lesiones por Gases Irritantes (LGI)*. Se evaluaron: Índice Trauma Pediátrico (ITP), APACHE II, características demográficas, estadía en TI (ETI), déficit de base en las 48 hs (DB/48) y mortalidad (M). Resultados. De los 5 pts (2 mujeres y 3 hombres), la edad promedio fue 8,6 años (rango 3-16), el APACHE II (promedio): 24.6 puntos (rango 2230), la ETI (promedio): 11,6 días (rango 1-18), ITP (promedio): 0 (-4 a +4) y el DB 48 (promedio) 11.4 mEq (rango -6 a -19). La mortalidad global fue del 40%. Tres pacientes presentaron LTVA, A y LGI, mientras que los dos restantes presentaron LTVA y A. Conclusión. La recepción de los 5 pts superó, en forma inmediata, los recursos en el sistema local hospitalario, cumpliendo con la definición de desastre. La acidosis metabólica durante las primeras 48 hs en el contexto del SIH se acompañó de mayor morbimortalidad.(AU)

How many victims are necessary to define a disaster? Objective. Describe a situation of care of multiple victims. Analyse the particular characteristics of smoke inhalation syndrome (SIH). Material and methods. 5 patients (pt) admitted to the Emergency Service of HRRG in November 2006 were evaluated. Three patients were admitted to the Intensive Care Unit, the only Service in the northern province of Tierra del Fuego. The Intensive Care Unit has 5 beds and 5 critical care ventilators to assit patients with respiratory failure. We admitted roughly 300 patients each year. The reasons for the admision were: Smoke inhalation Syndrome (SIH) and acute respiratory failure Injuries because inhaling smoke (LIH) were classified in: Thermal Injury of the Air (LTVA), Asphyxia (A) and Gas Injures Irritants (LGI). We consigned Pediatric Trauma Index (ITP), Apache II score, demographics, length of stay in STI, the basic deficit within 48 hours (DB/48) and mortality (M). Results. Of the 5 pt (2 women and 3 men), age was 8.6 years (range 3-16), the Apache II: 24.6 (range 22-30), length of stay 11.6 days (range 1-18), ITP: 0 (-4 to +4) and DB 48 (average) - 11.4 mEq (-6 to -19 range). The mortality rate was 40%. Three patients had LTVA, A and LGI, while the remaining two, both presented LTVA and A Conclusion. The admission of the 5 pt exceeded, immediately, resources in the local hospital system, fulfilling with the definition of disaster. The metabolic acidosis during the first 48 hours in the context of SIH was associated with increased morbidity and mortality(AU)

Interruption of antiretroviral treatment in HIV-infected patients with preserved immune function is associated with a low rate of clinical progression: a prospective study by AIDS Clinical Trials Group 5170.

BACKGROUND: We sought to determine the safety of treatment interruption (TI) and to identify parameters that would define patients with human immunodeficiency virus (HIV) for whom TI is safer. METHODS: AIDS Clinical Trials Group 5170 was a multicenter, 96-week-long, prospective study of HIV-infected patients receiving antiretroviral therapy (ART) who had CD4(+) cell counts >350 cells/mm(3) and who underwent TI. RESULTS: A total of 167 patients were enrolled. The median nadir in CD4(+) cell count was 436 cells/mm(3). The initial decrease (i.e., during the first 8 weeks) in CD4(+) cell count after ART interruption was 20 cells/mm(3)/week; the subsequent decrease was 2.0 cells/mm(3)/week until week 96. Both the CD4(+) cell count before enrollment and the increase in CD4(+) cell count during ART predicted early decrease; later decrease was predicted by the level of interleukin-7 at enrollment. A Centers for Disease Control and Prevention (CDC) diagnosis of a category B or C event was made for 2 and 2 patients, respectively (all had CD4(+) cell counts >350 cells/mm(3)). At week 96, 17 patients had CD4(+) cell counts < or =250 cells/mm(3), and 46 patients had resumed ART; 5 patients died (unrelated to HIV or acquired immunodeficiency syndrome). In a multivariate analysis, a higher nadir in CD4(+) cell count (>400 cells/mm(3)), a lower HIV load (<50 copies/mL) at the time of TI, and an HIV load < or =22,000 copies/mL before ART predicted a longer time to the primary end point (CDC category B or C event, death, CD4(+) cell count < or =250 cells/mm(3), or resumption of ART). CONCLUSION: Disease progression after TI was low in this cohort. A higher nadir in CD4(+) cell count, a lower HIV load before ART, and an HIV load < or =50 copies/mL at the time of TI predicted a longer time to the primary end point.

[Survival of patients with myasthenia gravis after thymectomy. Analysis of 100 cases]. / Supervivencia en pacientes con miastenia gravis después de la timectomía. Análisis de 100 casos.

In order to evaluate the survival of patients with myasthenia gravis (MG) after thymectomy (T), 100 patients with MG in which T had been performed between 1967 and 1995 were studied. Patients were divided into different groups for their analysis: patients with thymoma (TI), 22 cases; and patients without thymoma (NTI), 78 cases. In addition those patients belonging to the latter group were further separated according to the date of their surgery into two other subgroups: patients operated before 1980 (A80), 43 cases; and after 1980 (D80), 35 cases; trying to evaluate the prognostic implications of the therapeutical advances achieved over the last 15 years. The population studied was composed mainly of women (78%) but with a slight predominance of men in TI. The mean age was 29.47 years (range 10-70) for the entire population, with a tendency toward older ages in TI (mean 46 years, range 23-70). The mean follow-up period was 4.3 years (range 0.08-23.2) without significant differences between TI and NTI. The results showed that the overall mortality rate was 16/100 (16%) [Fig. 1], with nine of those deaths corresponding to TI (9/22, 40.91%) and only the remaining seven to NTI (7/78, 8.97%). These differences in mortality rate between TI and NTI were statistically significant in all the specific times of follow-up analyzed up to 10 years after surgery (p < 0.05) [Fig. 2]. Notoriously, all deaths in NTI occurred in the A80 subgroup giving a p value < 0.001 when compared with D80 [Fig. 3]. In terms of morbidity, 55/100 (55%) reached complete clinical remission (CCR) defined by the complete absence of symptoms related to MG: 8/22 (36.36%) in TI and 47/78 (60.25%) in NTI [Fig. 4]. Most interestingly the differences were statistically significant (p < 0.01) when the rates of CCR in A80 and D80 were compared for all the times assessed [Fig. 5-6-7-8]. It can be concluded that the best results in survival in MG after T are obtained in patients without thymoma and also that the benefits of the rational use of modern therapeutic modalities, including surgery and immunosuppression with drugs, can offer those patients high possibilities of leading completely normal lives.

Supervivencia en pacientes con miastenia gravis despues de la timectomia: analisis de 100 casos / Survival of patients with myasthenia gravis after thymectomy: analysis of 100 cases

Con la finalidad de evaluar la supervivencia de paciente con miastenia gravis (MG) después de la timectomía (T), se estudiaron 100 personas afectadas por la enfermedad y operadas entre 1967 y 1995, al mes (M1), al año (A1), a los cinco (A5) y a los diez años (A10). Se empleó para este análisis el método de Kaplan-Meier y la prueba de Log-rank para las comparaciones. Los pacientes fueron clasificados de acuerdo a los hallazgos anatomopatológicos tras la T en un grupo con timoma (TI) con 22 casos y otro sin timoma (NTI) con 78 casos. La supervivencia de TI y NTI fue 95 + 5 por ciento y 94 + 3 por ciento, respectivamente en M1; 70 + 10 por ciento y 92 + 4 por ciento en A1; 47 + 17 por ciento y 87 + 5 por ciento en A5 y A10 (p < 0,05 para las tres últimas diferencias). Para reconocer la implicancia de los avances terapéuticos sobre la supervivencia, se dividió al grupo NTI en dos subgrupos: operados antes de 1980 (A80) con 43 casos y después de ese año (D80) con 35 casos. La sobrevida de A80 fue 88+ 5 por ciento en M1,84 + 6 por ciento en A1 y 77+8 por ciento en A5 y A10; no hubo muertes en D80 en el seguimiento hasta 10 años (p < 0,01). Estos datos confirman que los mejores resultados de supervivencia en MG después de T se dan en casos sin timoma así como la inobjetable superación del tratamiento de la enfermedad en los últimos 15 años con cuidados intensivos y uso de inmunosupresores.

Supervivencia en pacientes con miastenia gravis despues de la timectomia: analisis de 100 casos / Survival of patients with myasthenia gravis after thymectomy: analysis of 100 cases

Con la finalidad de evaluar la supervivencia de paciente con miastenia gravis (MG) después de la timectomía (T), se estudiaron 100 personas afectadas por la enfermedad y operadas entre 1967 y 1995, al mes (M1), al año (A1), a los cinco (A5) y a los diez años (A10). Se empleó para este análisis el método de Kaplan-Meier y la prueba de Log-rank para las comparaciones. Los pacientes fueron clasificados de acuerdo a los hallazgos anatomopatológicos tras la T en un grupo con timoma (TI) con 22 casos y otro sin timoma (NTI) con 78 casos. La supervivencia de TI y NTI fue 95 + 5 por ciento y 94 + 3 por ciento, respectivamente en M1; 70 + 10 por ciento y 92 + 4 por ciento en A1; 47 + 17 por ciento y 87 + 5 por ciento en A5 y A10 (p < 0,05 para las tres últimas diferencias). Para reconocer la implicancia de los avances terapéuticos sobre la supervivencia, se dividió al grupo NTI en dos subgrupos: operados antes de 1980 (A80) con 43 casos y después de ese año (D80) con 35 casos. La sobrevida de A80 fue 88+ 5 por ciento en M1,84 + 6 por ciento en A1 y 77+8 por ciento en A5 y A10; no hubo muertes en D80 en el seguimiento hasta 10 años (p < 0,01). Estos datos confirman que los mejores resultados de supervivencia en MG después de T se dan en casos sin timoma así como la inobjetable superación del tratamiento de la enfermedad en los últimos 15 años con cuidados intensivos y uso de inmunosupresores. (AU)

Tempo de internaçäo na UTI pediátrica de Botucatu - Unesp, de acordo com os critérios preditivos / Lenght of stay in pediatric critical care from Botucatu - Unesp, relationship to predictive criteria

Em nove meses foram internados 192 pacientes na UTI pediátrica da UNESP, 61,1 por cento do sexo masculino. Os pacientes maiores de um ano tiveram maior mortalidade (14,5 por cento - n = 110) em relaçäo aos lactentes (9,1 por cento - n = 76), com sete internaçöes neonatais. Os pacientes com Distúrbios Respiratórios (DR - n = 43) foram os que necessitaram de maior tempo de internaçäo (TI = 15,2 + 15,8 dias), seguido dos Sépticos (S - n = 60 - TI = 7,8 + 4,8 dias). Os óbitos tiveram maior instabilidade fisiológica e pioraram mais (PRISM Admissäo A = 24,6 + 10,7; M ximo M = 33,6 + 9,8; e no Ultimo dia U = 31,8 + 11,9) que os sobreviventes (A = 16,2 + 7,5; M = 16,5 + 9,2; U = 3,0 + 3,4), necessitando de maior intervençao terapêutica (TISS Ob. A = 44,6 + 9,8; M = 51,2 + 15,7; U = 46,7 + 10,3 - Sob. A = 37,6 + 7,9; M = 40,2 + 6,9; U = 15,8 + 8,3). Na faixa < 10 do escore PRISM näo tivemos nenhum óbito e o tempo de internaçäo foi de 3,3 + 1,5 dias, com aumento da mortalidade e o do tempo de permanência na unidade até o escore de 21 a 30 (22,7 por cento mortalidade, TI = 10,7 + 7,2 dias) e com escore > 30 com mortalidade de 70 por cento e TI = 5,4 + 4,7 dias. No escore de intervençäo terapêutica TISS na faixa < 35 näo tivemos óbito, e o aumento da necessidade desta intervençäo acarretou um maior tempo de internaçäo, sendo máximo com escore > 45 (TI = 10,0 + 8,0 dias e mortalidade de 45 por cento). A mortalidade prevista pelo PRISM em relaçäo à mortalidade real foi que 0,7 por cento dos 146 pacientes com mortalidade prevista menor que 30 por cento faleceram, enquanto que 80 por cento dos 20 pacientes com mortalidade prevista maior que 60 por cento faleceram. O coeficiente de mortalidade total foi de 11,4 por cento. Concluímos ser importante o uso desses escores preditivos em todas UTIP, como uma forma de controle de qualidade do serviço realizado, assim como para podermos comparar resultados em diversas unidades.

The role of thoracic and cranial irradiation for small cell carcinoma of the lung.

Since 1974, 120 previously untreated patients with small cell carcinoma of the lung seen in Therapeutic Radiology at The Medical College of Wisconsin have been entered into one of 4 successive studies. Study I used thoracic irradiation (TI) alone (4500-6000 rad in 3-6 weeks) with chemotherapy at progression. Study II randomized patients with limited disease to TI (3000 rad in 2 weeks) plus either cyclophosphamide, doxorubicin, vincristine (CAV) or total body irradiation (TBI); patients with extensive disease received TI + CAV. Study III employed prophylactic cranial irradiation (PCI) plus CAV and withheld TI unless there was incomplete response or recurrence. Of 93 evaluable patients from the first three studies, 55 had limited and 38 extensive disease. Study I (37 patients) showed a 62% complete response (CR) rate; 43% failed in the chest, 14% had brain metastases, and the median survival was only 22 weeks in spite of a preponderance of limited disease patients. Study II (27 patients) showed a CR of 59%; 30% had brain metastases and the median survival was 48 weeks. Study II patients (29) had a 69% rate; 72% failed in the chest, 4% with PCI developed brain metastases, and the median survival was 50 weeks. In March, 1979, Study IV was initiated; patients receive PCI (2500 rad in 2 weeks) plus high dose CAV, methotrexate and leucovorin. After 6 cycles, consolidation TI (3750 rad in 3 weeks) is given to patients with complete response. Preliminary results with 27 patients treated on this study show a 67% CR rate, a 41% chest failure rate (but only 11% for the patients who received thoracic irradiation) and no intracranial failures, but a 13% extracranial CNS failure rate. PCI, TI and spinal irradiation may be necessary to maximize the probability of long term disease free survival.