Medical management of small uterocutaneous fistulae with gonadotrophin releasing hormone analogs: Case report and literature review.

Conventional management of uterocutaneous fistula involves open or laparoscopic excision as well as hysterectomy but there is now increasing recognition of successful medical treatment with gonadotrophin releasing hormone agonists. We describe the fourth case in the literature of successful nonsurgical treatment of uterocutaneous fistula and discuss two important factors affect the success of medical management, namely the size of the fistula and the duration of treatment. We would recommend that a trial of gonadotrophin releasing hormone analogues for at least 6 months particularly in cases of uterocutaneous fistula of 5 mm or less in diameter as this conservative treatment is likely to obviate the need for more hazardous surgical intervention.

Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap).

Ischemic retinal dystrophies are leading causes of acquired vision loss. Although the dysregulated expression of the hypoxia-responsive VEGF-A is a major driver of ischemic retinopathies, implication of additional VEGF-family members in their pathogenesis has led to the development of multivalent anti-angiogenic tools. Designed as a decoy receptor for all ligands of VEGFR1 and VEGFR2, Aflibercept is a potent anti-angiogenic agent. Notwithstanding, the molecular mechanisms mediating Aflibercept's efficacy remain only partially understood. Here, we used the oxygen-induced retinopathy (OIR) mouse as a model system of pathological retinal vascularization to investigate the transcriptional response of the murine retina to hypoxia and of the OIR retina to Aflibercept. While OIR severely impaired transcriptional changes normally ensuing during retinal development, analysis of gene expression patterns hinted at alterations in leukocyte recruitment during the recovery phase of the OIR protocol. Moreover, the levels of Angiopoietin-2, a major player in the progression of diabetic retinopathy, were elevated in OIR tissues and consistently downregulated by Aflibercept. Notably, GO term, KEGG pathway enrichment, and expression dynamics analyses revealed that, beyond regulating angiogenic processes, Aflibercept also modulated inflammation and supported synaptic transmission. Altogether, our findings delineate novel mechanisms potentially underlying Aflibercept's efficacy against ischemic retinopathies.

Real life outcomes of patients aged ≥75 years old with acute promyelocytic leukemia: experience of the PETHEMA registry.

Acute promyelocytic leukemia is infrequent among patients aged ≥75 years old, a population that is rarely eligible for clinical protocols. This study aims to analyze the treatment strategies and clinical outcomes of very old APL patients reported to the international PETHEMA registry. Between 1997 and 2017, among 2501 APL cases registered 120 were ≥75 years old. Treatment approaches were: AIDA regimen, 79 patients; ATRA alone, 23; 16, supportive care (SC) and 2, other strategies. Patients treated with AIDA were younger, had better ECOG and lower leukocytes. Complete remission (CR) was achieved in 65% of AIDA-group vs. 45% in the ATRA-group, being infections followed by bleeding the most frequent causes of induction death. Patients in CR after AIDA showed 3-year DFS of 73%. Our real-life series of very old APL patients provides a reference basis for future treatment strategies aiming to improve clinical outcomes in this challenging population.

Seroprevalencia de la infección por dengue en los municipios de Armenia, Calarcá, La Tebaida y Montenegro en el departamento del Quindío, 2014 / Seroprevalence of dengue infection in the municipalities of Armenia, Calarcá, La Tebaida and Montenegro in Quindío, 2014

Resumen Introducción: El dengue representa un grave problema de salud pública para Colombia y, en el departamento del Quindío, afecta el 90 % de los municipios. Se necesitan estudios actualizados sobre la seroprevalencia en la población general para reforzar las acciones de salud pública. Objetivo: Determinar la seroprevalencia de la infección por dengue en barrios con alta incidencia de dengue en cuatro municipios del departamento del Quindío: Armenia, Calarcá, La Tebaida y Montenegro, en 2014. Materiales y métodos: Se hizo un estudio de prevalencia mediante muestreo probabilístico estratificado y bietápico. Se hizo una encuesta a 658 sujetos residentes del área urbana de los municipios seleccionados y se les tomó una muestra de sangre por venopunción para determinar anticuerpos IgG e IgM contra el virus del dengue. Resultados: La seroprevalencia de anticuerpos IgG en el Quindío fue de 89,4 %; en Armenia fue de 88,7 %, en Calarcá, de 81,5 %, en Montenegro, de 91,8 %, y en La Tebaida, de 97,8 %. La seroprevalencia de anticuerpos IgM en Quindío fue de 14,2 %; en Armenia, de 11,5 %, en Calarcá, de 13,0 %, en Montenegro, de 13,1%, y en La Tebaida, de 28,9 %. Conclusiones: Se evidenció una alta prevalencia de anticuerpos IgG e IgM en los cuatro municipios. En todos los grupos de edad se encontraron personas seropositivas para IgM, lo cual indicaría infección reciente. La seropositividad simultánea para IgM e IgG (12,9 %) puede indicar infección secundaria por otro serotipo del virus o una infección en los tres meses anteriores. Es necesario impulsar estrategias multisectoriales para el control de la transmisión del dengue en el Quindío.

Abstract Introduction: Dengue is a serious public health problem in Colombia; it is prevalent in 90% of the municipalities in Quindío. Studies on its seroprevalence are required to address public health interventions. Objective: To establish the seroprevalence of dengue infection in neighborhoods with high incidence in the municipalities of Armenia, Calarcá, La Tebaida and Montenegro, Quindío, in 2014. Materials and methods: We conducted a probabilistic, stratified, two-stage prevalence study. We interviewed 658 residents in the urban area of the selected municipalities. After they signed the informed consent, we took a blood sample to determine dengue IgG and IgM antibodies. Results: Seroprevalence of IgG in Quindío was 89,4%; in Armenia it was 88,7%, in Calarcá, 81,5%, in Montenegro, 91,8% and in La Tebaida 97,8%. IgM was 14, 2% in Quindío; in Armenia it was 11,5%, in Calarcá, 13,0%, in Montenegro, 13,1% and in La Tebaida, 28,9%. Conclusions: We found a high prevalence of both IgG and IgM in the four municipalities. We had positive results for IgM in all age groups, which suggests recent infection. We also found simultaneous seropositivity for IgG and IgM (12.9%), which may indicate infection by another serotype or presence of infection in the past three months. A multisectoral approach is necessary for dengue control in Quindío.

Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients.

BACKGROUND: Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1-4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. METHODS: To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population. RESULTS: Patients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T > G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C > T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T > G); and 11.11%, 8.82% and 9.00% for T (c.458C > T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33. CONCLUSIONS: The novel loss-of function mutation of CTSC gene (c.203 T > G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.

Clinical significance of occult cerebrospinal fluid involvement assessed by flow cytometry in non-Hodgkin's lymphoma patients at high risk of central nervous system disease in the rituximab era.

BACKGROUND AND AIM: Flow cytometry (FCM) analysis of cerebrospinal fluid (CSF) is more sensitive than conventional cytology (CC) for diagnosis of lymphomatous meningeosis, but the clinical significance of occult central nervous system (CNS) disease (positive FCM with negative CC) remains unknown. PATIENTS AND METHODS: CSF samples from 105 patients with newly diagnosed aggressive lymphomas at high risk of CNS involvement were prospectively studied by both CC and FCM, and results were correlated with cumulative incidence of CNS relapse and overall survival (OS). Patients were divided into three groups: 1) patients without CNS involvement (CC-/FCM-; n=83); 2) individuals with occult CNS disease (FCM+/CC-; n=15); and 3) cases with CNS disease (CC+/FCM+; n=7). RESULTS: Six cases showed CNS relapse or progression: two in Group 1 (2.4%), two in Group 2 (13%) and two in Group 3 (28.5%) (Group 2 vs. 1, P=0.04; Group 3 vs. 1, P<0.001). Patients from Groups 2 (P=0.05) and 3 (P<0.001) also showed a higher cumulative incidence of CNS relapse than those from Group 1. Significant differences were observed in OS between FCM-/CC- and FCM+/CC+ cases (P=0.02), while patients with occult CNS disease (FCM+/CC-) displayed intermediate OS rates, although differences did not reach statistical significance. CONCLUSIONS: The presence of occult CNS involvement at diagnosis in patients with NHL at high risk of CNS disease is associated with a higher probability of CNS relapse.

Costochondral graft with green-stick fracture used in reconstruction of the mandibular condyle: experience in 13 clinical cases.

Since its publication in 1920 by Gillies, costochondral grafts have been used by surgeons to replace and injured mandibular condyle and to reconstruct the temporomandibular joint. This procedure is currently applied in cases of congenital dysplasia, developmental defects, temporomandibular ankylosis, neoplastic disease, osteoarthritis and post-traumatic dysfunction. Over the years, various procedures for the reconstruction with this type of graft have been described. In 1989, Mosby and Hiatt described a technique for setting the graft securely, reducing the space between the graft and the mandibular area. In 1998, Monje and Martín-Granizo developed a variation of this method, enabling a precise adaptation of the costochondral graft to the remaining mandibular ramus. The aim of this study is to evaluate the functional and anatomic results of the costochondral graft treatment by green-stick fracture for reconstruction of the TMJ in the 10 years following the description of this technique. We carry out a retrospective study of thirteen cases of temporomandibular pathology (tumors, ankylosis and hypoplasia) treated during a period of ten years from 1998 to 2008. In all these cases, the technique described by Monje and Martín-Granizo was used: removal of the sixth rib, fixation to a titanium mini-plate using screws, making an internal corticotomy in order to obtain a green-stick fracture of the outer cortex, providing adequate adaptation of the graft to the mandibular ramus. The graft was then set in place, attaching it with titanium screws. This technique was successful in achieving optimal ossification, a good interincisal opening and satisfactory cosmetic results. In conclusion, according to our experience, the green-stick fracture for the adaptation of costochondral grafts to the remaining mandibular ramus has presented outstanding results in the surgical treatment of temporomandibular pathology.

Metastasis of renal clear-cell carcinoma to the oral mucosa, an atypical location.

The majority of cases of metastatic tumors involve the mandible and some the maxilla but they are considerably less common in intraoral soft tissues. In addition, the primary tumor is known in the majority of cases; although in one-third of such cases, metastasis is the first clinical manifestation. The most common primary tumors metastasizing to the mouth are lung carcinoma in men and breast carcinoma in women. An oral metastasis implies a serious prognosis, as in the majority of patients there is multiple organ involvement at the time of diagnosis. We present the case of a 52-year old patient with renal pathology who came to the emergency room due to a rapidly increasing gingival tumor. With the provisional clinical diagnosis of a pyogenic granuloma,the tumor was excised. Subsequent anatomopathological analysis revealed a tumor metastasis compatible with clear-cell carcinoma, and its renal origin was confirmed by means of immunohistochemical techniques.

Identification of leptomeningeal disease in aggressive B-cell non-Hodgkin's lymphoma: improved sensitivity of flow cytometry.

PURPOSE: Here, we evaluate the sensitivity and specificity of a new 11-parameter flow cytometry (FCM) approach versus conventional cytology (CC) for detecting neoplastic cells in stabilized CSF samples from newly diagnosed aggressive B-cell non-Hodgkin's lymphoma (B-NHL) at high risk of CNS relapse, using a prospective, multicentric study design. PATIENTS AND METHODS: Moreover, we compared the distribution of different subpopulations of CSF leukocytes and the clinico-biologic characteristics of CSF+ versus CSF-, patients, in an attempt to define new algorithms useful for predicting CNS disease. RESULTS: Overall, 27 (22%) of 123 patients showed infiltration by FCM, while CC was positive in only seven patients (6%), with three other cases being suspicious (2%). CC+/FCM+ samples typically had more than 20% neoplastic B cells and/or >or= one neoplastic B cell/microL, while FCM+/CC- samples showed lower levels (P < .0001) of infiltration. Interestingly, in Burkitt lymphoma, presence of CNS disease by FCM could be predicted with a high specificity when increased serum beta2-microglobulin and neurological symptoms coexisted, while peripheral blood involvement was the only independent parameter associated with CNS disease in diffuse large B-cell lymphoma, with low predictive value. CONCLUSION: FCM significantly improves the sensitivity of CC for the identification of leptomeningeal disease in aggressive B-NHL at higher risk of CNS disease, particularly in paucicellular samples.

Tetralogy of Fallot associated with macrocephaly-capillary malformation syndrome: a case report and review of the literature.

INTRODUCTION: Macrocephaly-capillary malformation syndrome is characterized by cutaneous vascular lesions, including cutis marmorata telangiectatica and hemangiomas, associated with congenital anomalies, including macrocephaly, macrosomia, asymmetry and mental retardation. In addition to these cardinal signs, several other clinical conditions have been reported in people with this condition. However, to the best of our knowledge, the presence of tetralogy of Fallot has not previously been reported in association with this syndrome. CASE PRESENTATION: We present a case of a Mexican newborn girl with tetralogy of Fallot associated with macrocephaly-capillary malformation. We discuss the clinical treatment of the patient and its consequences. CONCLUSION: Since physiologic cutis marmorata is a common condition in newborns, the information provided in this report could be helpful in future cases in preventing severe clinical consequences or sudden death in patients with similar symptoms.

Tifus murino en el Cairo- Valle ¿Brote o condición endémica emergente? / Murine typhus in el Cairo, Valle ¿outbreak or emerging diseases?

Introducción: En el Municipio de El Cairo Valle se reportó un brote de Tifus Murino, el cual habitualmente no se diagnostica en la región. Métodos: Se presenta una serie de casos obtenidos del Sitema de Vigilancia Epidemiológica del Municipio de El Cairo, administrado por el Hospital Municipal. Resultados: Se reportan 34 casos nuevos de Tifus Murino, que como característicasespeciales fueron predominantemente femeninos, y población adulta. Conclusión: El brote fue controlado con la oportuna intervención del Comité de Vigilancia Epidemiológica del Municipio y coordinado por diferentesinstituciones.

[Prevalence and prognostic significance of myeloid markers in adults with high-risk acute lymphoblastic leukemia]. / Prevalencia y significado pronóstico de los marcadores mieloides en adultos con leucemia aguda linfoblástica de alto riesgo.

BACKGROUND AND OBJECTIVE: The prognostic value of myeloid antigen expression in adult acute lymphoblastic leukemia (ALL) is controversial. The objective of this study was to evaluate the frequency and prognostic significance of myeloid antigen expression in adults with high risk ALL. PATIENTS AND METHOD: Between June 1993 and July 2002, 222 adults patients with high-risk ALL were treated according to the PETHEMA LAL 93 protocol. The frequency of myeloid antigen expression, its association with other clinical and biologic variables and the prognostic significance in terms of complete remission (CR) rate, event free survival (EFS) and overall survival (OS) were analyzed. RESULTS: Myeloid antigen expression was present in 96 out of 222 patients (43%). No association was observed between myeloid antigen expression and the main clinical and biologic characteristics of ALL. Response to treatment was slower in patients expressing myeloid antigens, but no differences were found in CR achievement, EFS or OS. The probability of EFS at 10 years for ALL patients without and with myeloid antigen expression was 35% and 34%, respectively, while the probability of OS at 10 years was 30% and 33%, respectively. This absence of differences in EFS and OS probabilities was also observed when only slow responding patients were analyzed. CONCLUSIONS: In this study, myeloid antigen expression did not have prognostic influence in adult patients with high risk ALL.

All-trans retinoic acid and anthracycline monochemotherapy for the treatment of elderly patients with acute promyelocytic leukemia.

Therapeutic results in elderly patients with acute promyelocytic leukemia (APL) have been generally reported as less effective than for younger patients. Patients 60 years or older with APL who were enrolled in 2 successive multicenter PETHEMA studies received induction therapy with all-trans retinoic acid (ATRA) and idarubicin, consolidation with 3 anthracycline monochemotherapy courses with or without ATRA, and maintenance with ATRA and low-dose chemotherapy. Eighty-seven of 104 patients achieved complete remission (84%). Eighty-six proceeded to consolidation therapy (2 withdrew after the first and second courses). Deaths in remission occurred during consolidation and maintenance therapy in 3 and 4 patients, respectively. One patient showed molecular persistence after consolidation and 5 had a relapse. The 6-year cumulative incidence of relapse, leukemia-free survival, and disease-free survival were 8.5%, 91%, and 79%, respectively. A significantly higher incidence of low-risk patients found among the elderly, as compared to younger patients, may partially account for the low relapse rate observed. This study confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of protocols using ATRA and anthracycline monochemotherapy for induction and consolidation therapy in elderly patients.

Amyloidosis of the submaxillary gland.

Amyloidosis can be defined as an extracellular deposit of the amyloid fibrillar protein in one or more locations in the organism. Multiple clinical and biochemical forms of amyloid exist, and are characterized according to their fibrillar structural characteristics. The Red Congo stain presents green fluorescence when histologic cuts are observed by polarized light. The deposits of this substance can be focal in nearly any area of the organism, although the perivascular space tends to be affected. We present the case of a woman operated on for myeloma at the base of the cranium who showed no wider affectation at a later study. Fourteen years after the operation the patient showed a progressive growth of the submandibular gland that was diagnosed as a pathological amyloid deposit.

Prognostic value of karyotypic analysis in children and adults with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 trial.

BACKGROUND AND OBJECTIVES: Cytogenetic analysis is one of the most reliable prognostic factors in acute lymphoblastic leukemia. The objective of this study was to analyze the prognostic value of cytogenetic analysis in children and adults with high-risk acute lymphoblastic leukemia (HR-ALL) included in a prospective multicenter trial. DESIGN AND METHODS: One hundred and thirty patients (44 children and 86 adults) with HR-ALL included in the PETHEMA ALL-93 trial had an adequate cytogenetic study after review. Cytogenetic subgroups were established according to the cancer and acute leukemia group B criteria (unfavorable: 11q23, t(9;22), -7 and +8; normal; miscellaneous: the remaining chromosome abnormalities) and their main clinicobiological features were compared. Univariable and multivariable analyses for complete remission (CR) attainment, event-free survival (EFS) and overall survival (OS) were performed. RESULTS: The mean SD age was 26 14 years. Two were infants (<1 year), 42 were children and 86 adults (19-50 years). The cytogenetic study was normal in 44 (34%) cases. The most frequent chromosomal rearrangement was t(9;22)(q34;q11) (34 cases, 26%, 30 adults), followed by 11q23 (12 cases, 9% -8 children-, including t(4;11)(q21;q23) in 8, 7 children). Patients with t(9;22) were older than the remaining cases, whereas those with 11q23 rearrangements were younger and had higher WBC counts. Multivariable analyses showed two associated factors in adults with a lower frequency of CR and a shorter EFS and OS: t(9;22) and slow response to therapy (assessed by a percentage of blast cells higher than 10% in bone marrow study on day 14). For children with very high-risk ALL, only slow response to therapy (assessed by the presence of blast cells in peripheral blood on day 8) was associated with a negative impact on CR, EFS and OS. INTERPRETATION AND CONCLUSIONS: In adult patients with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 protocol, cytogenetic analysis at diagnosis is a useful independent prognostic marker. The poorest prognosis for patients with t(9;22) justifies the development of specific treatments for these patients. In this small subgroup of children with very high-risk ALL no cytogenetic characteristics was found to influence the results of therapy, slow response to therapy being the only prognostic factor.

Estudio de las interacciones medicamentosas en un servicio de terapia intensiva / Pharmacological interactions study in the service of intensive care

La inclusión de pacientes en Unidades de Cuidados Intensivos indica su estado crítico de salud, requiriendo la coadministración de múltiples medicamentos, estableciéndose numerosas interacciones medicamentosas, que pueden dar lugar a efectos beneficiosos o perjudiciales. Se estudiaron cincuenta casos al azar de la Unidad de Cuidados Intensivos del Centro Policlínico Valencia, analizándose los efectos de la terapéutica en órganos y sistemas. Resultados: el sexo masculino representó 60 por ciento. La edad promedio 64.68 años, con mayor porcentaje entre 70 y 79 años y edades límites entre 28 y 89 años. En el 70 por ciento de los casos se detectó interacciones medicamentosas y en un 30 por ciento no. 58 por ciento de las interacciones fueron farmacodinámicas y 42 por ciento farmacocinéticas, las interacciones perjudiciales se presentaron en 68 por ciento, los sistemas más afectados por éstas fueron el Cardiovascular, Neurológico y Gastrointestinal

Diagnóstico por imagen de las metástasis raquimedulares / Diagnosis by image of the metastasis raquimeds

Expone el desarrollo de nuevos métodos de diagnóstico, actualmente nos permite evaluar las lesiones metastásicas que se presentan en la columna vertebral y la médula espinal. Presentamos la revisión de casos clínicos de los años 1996 y 1997, de pcientes que asisten a nuestro Instituto, resltando parámetros importantes como la edad, localización regional más frecuente, entre otros aspectos. Si bien la radiografía convecional y la mielografía nos ayudan a identificar el aspecto y compromiso que presentan las metástasis, estos estudios actualmente han sido sistituidos en gran parte por la tomografía computada e imajen por resonancia magnética. La tomografía computada nos proporciona datos específicos del componente óseo como son las erosiones óseas corticales, fracturas patológicas, depósitos calsificados, desorganización del hueso trabecular. La mayor sensibilidad en estudios de imajen corresponde a imajen por resonancia magnética, la cual nos permite valorar la infiltración metastásica de la médula ósea, compresión medular, además, permite obtener cortes axiales, sagitales y coronales. El uso de meidos de contraste paramagnéticos ayudan a identificar otras características de estas lesiones.

Determinacion de la longitud ideal de insercion de los cateteres subclavios / Length of insertion of subclavion catheters: a cadaveric study

Las complicaciones secundarias a la posición inadecuada de la "punta" de los catéteres venosos centrales, cuya incidencia real se desconoce, se asocia a una elevada morbimortalidad; por esta razón, la FDA (Food and Drug Administration) recomienda que la punta se localice siempre en la Vena Cava Superior (ves), objetivo que no se cumple en el 24 por ciento de las inserciones realizadas, según reportes de la literatura mundial. No existe ningún trabajo publicado en la actualidad que describa la longitud de inserción requerida para que la punta de los catéteres subclavios se aloje siempre en la vena cava superior. Con el fin de resolver este interrogante, se diseñó un estudio descriptivo en cadáveres donde se midió esta longitud, y se relacionó con algunos parámetros antropométricos. Las variables recolectadas se analizaron utilizando el programa estadístico spss/pc; para las variables continuas se utilizó la comparación de medianas (Método de Mann Withney), en tanto que para las variables discretas se utilizó Chi-cuadrado con corrección de Yates. Se encontró que el único parámetro estadísticamente significativo es el lado de inserción (longitud lado derecho: 14 cm, DE = 1.25 cm; lado izquierdo: 16 cm; DE = 1.25 cm; p < 0.05). Finalmente, se concluye que se debe utilizar en la inserción de los catéteres subclavios una longitud de 14 cm para el lado derecho y de 16 cm para el lado izquierdo; con el uso de estas medidas más del 95 por ciento de las "puntas" de los catéteres colocados por vía subclavia quedarán alojadas en la v c s, evitando así las complicaciones derivadas de la posición inadecuada