Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents.

AIM: To assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. METHODS: We ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95 years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. RESULTS: Detected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% - measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% - consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% - use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% - use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% - reassessment of patient's condition; acute exacerbation of COPD 0.8% - defer test until acute episode is over; severe asthma 0.4% - do not perform test; methylxanthine ingestion 0.3% - avoid consumption previously; other 6.1% - evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was canceled due to absolute contraindications in 2.9% of the requests. CONCLUSIONS: Working in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Ectima gangrenoso, manifestación cutánea infrecuente de una infección por diversos agentes / Ecthyma gangrenosum, a rare cutaneous manifestation of infection by various agents

El ectima gangrenoso es un trastorno infeccioso infrecuente clásicamente relacionado a bacteriemia, descrito principalmente en poblaciones inmunodeprimidas. El agente más comúnmente relacionado es Pseudomonas aeruginosa, sin embargo, se han descrito otras etiologías bacterianas, hongos filamentosos y levaduras. Su patogénesis está dada por la invasión de la pared de los vasos sanguíneos, causando trombosis arterial y venosa, desencadenando necrosis de epidermis y tejidos subdérmicos. Clínicamente, se manifiesta como máculas, vesículas o pústulas hemorrágicas que evolucionan a úlceras de superficie necrótica rodeadas por un halo eritematoso característico, habitualmente en un contexto clínico de sepsis. El diagnóstico de este cuadro es clínico, sin embargo, el estudio microbiológico es clave en la identificación del agente etiológico y un posterior tratamiento dirigido. En su manejo es esencial una alta sospecha clínica y el inicio de tratamiento antibiótico en forma precoz. La duración del tratamiento es variable y en algunos casos debe asociarse a debridación quirúrgica. El pronóstico es variable dependiendo de múltiples factores: estado inmunológico, agente etiológico, presencia de sepsis y el tiempo de inicio de tratamiento.(AU)

Ecthyma gangrenosum is an infrequent infectious disorder classically related to bacteremia, described mainly in immunosuppressed populations. The most related agent is Pseudomonas aeruginosa, however other bacterial etiologies, filamentous fungi and yeasts have been described. Its pathogenesis is given by the invasion of the blood vessel wall, causing arterial and venous thrombosis, triggering necrosis of epidermis and subdermal tissues. Clinically, it manifests as hemorrhagic macules, vesicles or pustules that evolve into ulcers with a necrotic surface surrounded by a characteristic erythematous halo, usually in a clinical setting of sepsis. The diagnosis of this condition is clinical, however the microbiological study is key in the identification of the etiological agent and a subsequent directed treatment. In its management, a high clinical suspicion and an early start of antibiotic treatment are essential. The duration of treatment is variable and in some cases it must be associated with surgical debridement. The prognosis is variable depending on multiple factors: immunological status, etiological agent, presence of sepsis and time of initiation of treatment.(AU)

A B-Cell-Specific Enhancer Orchestrates Nuclear Architecture to Generate a Diverse Antigen Receptor Repertoire.

The genome is organized into topologically associated domains (TADs) that enclose smaller subTADs. Here, we identify and characterize an enhancer that is located in the middle of the V gene region of the immunoglobulin kappa light chain (Igκ) locus that becomes active preceding the stage at which this locus undergoes V(D)J recombination. This enhancer is a hub of long-range chromatin interactions connecting subTADs in the V gene region with the recombination center at the J genes. Deletion of this element results in a highly altered long-range chromatin interaction pattern across the locus and, importantly, affects individual V gene utilization locus-wide. These results indicate the existence of an enhancer-dependent framework in the Igκ locus and further suggest that the composition of the diverse antibody repertoire is regulated in a subTAD-specific manner. This enhancer thus plays a structural role in orchestrating the proper folding of the Igκ locus in preparation for V(D)J recombination.

Safety of regadenoson in patients with severe chronic obstructive pulmonary disease.

OBJECTIVE: To assess the safety of regadenoson, a selective agonist of A2A adenosine receptors, combined with low-level exercise in subjects with severe chronic obstructive pulmonary disease (COPD), referred for myocardial perfusion imaging (MPI). METHODS: We studied prospectively 12 male patients with severe COPD. Stress was 4min of low-level exercise with bolus injection of regadenoson (0.4mg) at 1.5min, followed by (99m)Tc-MPI agent injection. Demographics, medical history, lung medications, adverse events, oxygen saturation (SatO2), MPI findings for coronary artery disease (CAD), and changes in systolic blood pressure (SBP), and heart rate (HR) were registered. RESULTS: The observed adverse event profile of regadenoson was similar to that of patients with mild-moderate COPD. There was no clinical exacerbation of COPD. Adverse events were self-limiting: dyspnea (33.3%), fatigue (25.0%), chest pain, headache (16.7%, respectively), and gastrointestinal discomfort, dry mouth, flushing, feeling hot and dizziness (8.3%, respectively). 25.0% of patients did not report any symptoms. We observed significant increases in SBP and HR from baseline (142.6mmHg±22.3 vs 152.5mmHg±18.5, and 80 b.p.m.±18 vs 105 b.p.m.±22, respectively; p<0.05). CONCLUSIONS: Regadenoson combined with low-level exercise is safe and well tolerated in stable patients with severe COPD undergoing MPI.

Estabilización dinámica con ligamentoplastia interespinosa en discopatía degenerativa de columna vertebral lumbar / Dynamic stabilization with interspinous ligamentoplasty in degenerative discopaty of lumbar spine

El tratamiento de la Discopatía Degenerativa lumbar, mediante dispositivo suave de estabilización dinámica, con el uso de ligamento para reforzamiento interespinoso, altera favorablemente el movimiento y la transmisión de carga de un segmento vertebral, proporcionando estabilidad y previniendo la enfermedad del segmento adyacente. Por lo tanto se realiza un estudio prospectivo, longitudinal con 25 pacientes con edades comprendidas entre 15 y 58 años, con diagnóstico de Discopatia degenerativa lumbar; con estudios de imágenes previos con radiografias en proyección AP, lateral y laterales dinámicas además de Resonancia Magnética, con los cuales se confirmo el diagnóstico, al igual que control radiológico postoperatorio, a los que se les practico semihemilaminectomia mas discectomíamas foraminectomía mas ligamentoplastia interespinosa del segmento afectado y adyacentes. Se obtuvo como resultado mejoría clínica inmediata en la mayoría de los pacientes y con pronto reintegro a sus actividades habituales luego de la cirugía.

The treatment of lumbar degenerative discopaty, by means of a soft dynamic stabilization device, with the use of ligament for interspinous reinforcement, alter favorably the movement and load transmission of a vertebral segment, providing stability and preventing the disease of the adjacent segment. Therefore a prospectivelongitudinal study is carried out on 25 patients with ages ranging from 15 to 58 years, with a lumbar degenerative disease diagnosis; previous radiographicstudies in AP, lateral and dynamic-laterals projectionsand also Magnetic Resonance Imaging confirm the diagnosis, along with postoperative radiological controls. The patients received semi-hemilaminectomy plus discectomy plus foraminectomy plus interspinous ligamentoplasty of affected and adjacent segments. As result, inmediate clinical improvement in most patients was obtained and a soon return to their usual activities after the surgery.

[Quantitative salivary gland scintigraphy in head and neck cancer patients following radiotherapy]. / Gammagrafía salival cuantitativa en pacientes con cáncer de cabeza y cuello tratados con radioterapia.

OBJECTIVE: To assess the role of quantitative salivary gland scintigraphy (SGS) in the detection of functional impairment of salivary glands in patients with head and neck cancer treated with radiotherapy (RT). MATERIAL AND METHODS: We studied 19 patients (17 men), mean age 62.4 years (44-75). Three studies were performed to each patient: baseline, 3 and 18 months after RT. SGS was acquired for 25 minutes following injection of 3.7 MBq/kg of (99m)Tc-pertechnetate with lemon juice at the end of minute 15. Excretion fraction (EF), counts per minute/pixel/MBq (CMPM) and uptake percentage were obtained from time-activity curves from ROIs placed over parotid (PG) and submandibular glands (SMG) and related to the doses received by the PG. RESULTS: EF showed a significant reduction from the baseline to the 3 months study (p<0.001) for the PG and SMG and from the baseline to the 18 months study for the SMG (p<0.001). A significant improvement of EF was seen from the 3 months to the 18 months study for the PG (p<0.05). CMPM did not change significantly from the baseline to the 3 months and 18 months studies for the PG and showed a significant reduction (p<0.01) for the SMG from the baseline to 18 months study. The uptake percentage did not change significantly between studies. A moderate association was observed between the doses to PG and the 3m study parameters. CONCLUSIONS: EF was more sensitive than uptake in assessing post-RT impairment of salivary function. In addition, it reflected functional recovery of parotid glands over time.

Intravenous vitamin C as a chemotherapy agent: a report on clinical cases

A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma (2), Colorectal cancer (1), Pancreatic cancer (1), Non-Hodgkin's lymphoma (2) and breast cancer (1). Toxic reactions were not observed at these high doses of intravenous Vitamin C. All patients were prescreened for Glucose 6--phosphate dehydrogenase deficiency before administering intravenous Vitamin C in order to prevent hemolysis

Cell membrane fatty acid composition differs between normal and malignant cell lines

Twenty-eight fatty acids (C8:0 to C24:l n-9) were measured by gas chromatography in four normal cell lines (C3H / 10T1 / 2, CCD-18Co, CCD-25SK and CCD-37Lu) and seven cancer cell lines (C-41, Caov-3, LS-180, PC-3, SK-MEL-28, SK-MES-1 and U-87 MG). Results show differences in the content and proportions of fatty acids when comparing cancer cell lines with their normal counterparts. Cancer cell lines showed lower C20: 4 n-6, C24:1 n-9, polyunsaturated fatty acids (PUFA's) and ratios of C20:4 n-6 to C20:5 n-3 and C16:0 to C18:1 n-9 and stearic to oleic (SA/OA) than their normal counterparts. All cancer cell lines had SA/OA ratios lower than 7.0 while normal cell lines had ratios greater than 0.7 (p<0.05). In addition, the ratios of total saturated fatty acids (SFA) to PUFA'S and the concentration of C18:1 n-9, C18:2 n-6, C20:5 n-3 were higher in cancer cell lines as compared to normal cell lines. A positive correlation was detected between C16:0 and longer SFA'S (r = +0.511, p<0.05) in normal cell lines whereas a negative correlation (r=0.608, p<0.05) was obtained for malignant cell lines. Moreover, cancerous cell lines exhibited a particular desaturation defect and an abnormal incorporation of C18:2 n-6 and C20-4 n-6 fatty acids

[Characterization of neuronal ceroid lipofuscinosis in Venezuelan children]. / Caracterización de la ceroidolipofuscinosis en niños venezolanos.

INTRODUCTION: Neuronal ceroid lipofuscinosis (NCL), represents a group of inherited neurodegenerative disorders. Based on the age of the patient at onset, clinical course and ultrastructural morphology it has been identified three clinical types for the pediatric group: 1) Infantile NCL (INCL); 2) Late infantile NCL (LINCL); and 3) Juvenile NCL (JNCL). Other variants or atypical forms represent around 20% of the NCL in different populations. Genetic advances have made possible a better characterization, diagnostic and classification of these disorders. CASE REPORTS: We present the clinical, neurophysiological, neuroradiological, and morphological data from 6 patients with NCL, who were assessed at the pediatric neurology department of the Hospital Universitario de Maracaibo during a ten years period (1993 2003). All 6 cases corresponded with the late infantile form. Age of onset ranged form 2 to 5 years. For most of the patients initial symptoms included seizures, psychomotor delay, accompanied by macular degeneration and optic atrophy. The EEG was characterized by high voltage spikes elicited by low frequency photic stimulation, in 5 cases. Neuroimaging findings were characteristic of the late infantile form of the NCL. In three patients a decreased intensity of signal was seen in the thalami and putamen on T2-weighted images. The ultrastructural examination of the samples obtained through a biopsy showed curvilinear bodies in all patients. CONCLUSION: There is not epidemiological data of the NCL in Venezuela; it is presumed the presence of clinical forms and variants in the pediatric group. This first study could contribute to the knowledge and a better research of this group of disorders in our population.

Intravenous ascorbic acid: protocol for its application and use

High dose intravenous(i.v.) ascorbic acid (AA) has been used as therapy for infectious disease from bacterial and viral origin and adjuvant therapy for cancer. In this publication we describe a clinical protocol that has been developed over the past twenty years utilizing high dose i.v. AA as therapy for cancer. This includes principles of treatment, rationale, baseline workup, infusion protocol, precautions and side effects.

Efecto de la hormona de crecimiento recombinante humana sobre el sistema inmune de los niños / Effect of growth human hormone in inmune system in the childs

Trabajo prospectivo, abierto, experimental en el cual se incluyeron 16 pacientes con talla baja familiarpara valorar el efecto de la hormona de crecimiento (GH) sobre el sistema inmune. En conclusión, la aplicación de l aGH podría tener un efecto positivo sobre el sistema inmune

Experiencia en trauma renal en niños: Hospital Clínico San Borja Arriarán / Renal trauma experience in children: San Borja Arriarán Clinical Hospital

El tratamiento abdominal se ha convertido en un problema emergente y dentro de éste el órgano más frecuentemente lesionado este riñón. El objetivo de nuestro trabajo fue caracterizar epidemiológicamente y analizar la conducta terapéutica de los traumas renales ingresados a nuestro servicio. Se analizaron retrospectivamente las fichas clínicas de 42 pacientes ingresados por traumatismo abdominal complicado en el Servicio de Urgencia del Hospital San Borja Arriarán entre los años 1984 a 2001. De los pacientes con trauma renal se analizó la información referente a exámenes clínicos e imagenológicos, su clasificación, su tratamiento y complicaciones. De los 42 traumas abdominales hubo 13 casos con compromiso renal, los exámenes realizados fueron análisis de orina en todos los casos, ecografía renal en 9,TAC en 6 UIV en 5 angiografía renal en un caso. La frecuencia de las lesiones fue: 5 Grado 2, 1 Grado 3, 5 Grado 4, 1 Grado 5. La relación hombre mujer fue de 3,6: 1 con un promedio de edad de 9 años 6 meses, los mecanismos de lesión más frecuentes fueron caídas de altura, golpe directo y atropello (con 4 casos cada uno), el manejo fue expectante en 10 casos y de resolución quirúrgica de urgencia en 3. En 3 pacientes en que se mantuvo conducta expectante debió realizarse una cirugía electiva por complicaciones. Se realizaron 2 nefrectomías y una heminefrectomía. El promedio de estadía hospitalaria fue de 15 días, siendo 31 para los pacientes con cirugía y de 6 días para los que no quirúrgicos. Nuestro trabajo concuerda con la literatura en que el riñón más frecuentemente lesionado en los traumas abdominales. Existe una clara diferencia en cuanto al sexo, siendo el grupo más afectado los hombres entre 7 a 12 años. Dentro de los exámenes realizados, la ecografía es uno de los más solicitados. Se observa a través de los años analizados una tendencia hacia un manejo conservador para las lesiones renales.

Identificación y tipificación de levaduras aisladas de pacientes de un hospital de la ciudad de México / Identification and typing of yeast isolates from hospital patients in Mexico City

Nosocomial yeast infections have become a major cause of morbidity and mortality in immunocompromised patients. This study presents the frequency of yeasts isolated from different biological products from a Mexico City hospital's patients during one year. C. albicans was isolated in 72.3 of patients, followed by C. glabrata (13.4) and C. parapsilosis (8). Twenty different morphotypes were identified and the serotype B was the most frequent (79).

Open biliary tract surgery: multivariate analysis of factors affecting mortality.

BACKGROUND/AIM: The overall mortality rate in patients undergoing supraduodenal choledochotomy for benign biliary tract disease is around 3%. The aim of this study is to identify and quantify factors affecting the mortality in a group of patients undergoing open common bile duct exploration for benign biliary disease. METHODS: Patients (n = 158) who underwent common bile duct exploration during a 5-year period in a teaching hospital were retrospectively reviewed. RESULTS: Univariate and multivariate statistical analyses were performed. The former identified four statistically significant variables: age (p < 0.001), acute cholangitis on admission (p < 0. 001), heart disease (p < 0.05), and a dilated common bile duct on preoperative ultrasound scan (p < 0.05). Multivariate analysis identified three variables which independently increased operative mortality: age (p = 0.05), heart disease (p = 0.03), and cholangitis (p = 0.008). The latter was associated with the greatest operative mortality, since it increased almost eight times the risk to die after surgical intervention. CONCLUSION: We conclude that an adequate perioperative cardiovascular management may be important in order to improve surgical outcome. Appropriate antibiotic prophylaxis and subsequent treatment after routine operative bile cultures may reduce septic complications and mortality. Finally, an alternative procedure, such as endoscopic sphincterotomy, may be indicated in high-risk patients in order to drain the common bile duct preoperatively and to decrease the risk of unresponsive biliary sepsis.