Activity and safety of topical pimecrolimus in patients with early stage mycosis fungoides (PimTo-MF): a single-arm, multicentre, phase 2 trial.

BACKGROUND: The calcineurin pathway is often activated in mycosis fungoides. We aimed to assess the activity and safety of topical pimecrolimus, a calcineurin inhibitor, in patients with early mycosis fungoides. METHODS: PimTo-MF was a single-arm, multicentre, phase 2 trial done at six medical centres in Spain. Patients (aged ≥18 years) had histologically confirmed early mycosis fungoides (stages IA-IIA) and an Eastern Cooperative Oncology Group performance status of 0-1. Key exclusion criteria included the use of concurrent treatments for mycosis fungoides, including sunbathing, topical or systemic corticosteroids, and other calcineurin inhibitors. Patients applied topical pimecrolimus 1% cream on their skin lesions twice daily for 16 weeks (1 g per 2% of body surface), with subsequent follow-up of 12 months. Dosage modifications were not allowed. To evaluate adherence to the treatment, patients were instructed to return all empty tubes to the hospital (as per drug accountability protocols). The primary endpoint was the overall response ratein the intention-to-treat population. PimTo-MF is registered with EudraCT, 2014-001377-14, and is complete. FINDINGS: Between March 1, 2015, and Sept 30, 2016, 39 patients were enrolled. All patients were assessable, with a median age of 51·5 years (IQR 45-62), and the population was predominantly male (24 male [62%], 15 female [38%]). Median follow-up after baseline was 5·7 years (IQR 5·7-6·2). 22 (56%) of 39 patients had an overall response (one complete response, 21 partial responses). Responses were observed across IA (14 [54%] of 26 patients) and IB (eight [73%] of 11 patients) clinical stages, but not IIA. Topical pimecrolimus was well tolerated and no patient required a dose reduction or discontinued treatment because of unacceptable drug-related toxicity. No patients were lost to follow-up or discontinued treatment. 13 (33%) of 39 patients reported adverse events; transitory mild burning or pruritus (grade 1) was the most common, seen in eight (21%) patients. In three (8%) of these patients, the burning or pruritus was considered related to treatment. No grade 4 or 5 adverse events were observed. INTERPRETATION: Pimecrolimus 1% cream seems active and safe in patients with early stage mycosis fungoides. Our findings should be taken with caution until long-term follow-up data are obtained that confirm the safety of this treatment. Further controlled clinical trials are warranted to confirm these results. FUNDING: Instituto de Salud Carlos III and the European Regional Development Fund. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

A Replicable and Reproducible Digital Method for Quantifying Maxillary Sinus Airway Changes after Sinus Lifts Using the Lateral Window Approach Technique-A Retrospective Study.

In the present retrospective study, we aimed to assess the replicability and reproducibility of a novel digital measurement technique for analyzing the volumes of the left and right maxillary sinuses and the nasal and maxillary sinus airway complex after a sinus lift procedure using the lateral window approach, to provide an accurate measurement technique for easily applying in clinical practice and to allow pre-operative assessment of maxillary sinus lift surgery, avoiding complications and making surgery more predictable. MATERIAL AND METHODS: Thirty patients with partially edentulous posterior maxilla were selected and submitted to bilateral sinus lift using the lateral window approach technique, with grafting materials selected and submitted to cone beam computed tomography (CBCT) scans, both pre- and postoperatively. Then, datasets were uploaded to therapeutic digital planning software to measure the volume of the right and left maxillary sinuses and the nasal and maxillary sinus airway complex. Gage R&R statistical analysis was performed to assess the replicability and reproducibility of the digital measurement technique. RESULTS: The variability attributable to the novel digital measurement technique was 3.4% for replicability and 3.4% for reproducibility of the total variability of the samples. CONCLUSION: The novel digital method proposed is a replicable and reproducible technique for analyzing the volume of the right and left maxillary sinuses and the nasal and maxillary sinus airway complex after a sinus lift using the lateral window approach technique, allowing an accurate pre-operative assessment of maxillary sinus lift surgery, avoiding complications and making surgery more predictable.

Aberrant immunophenotypes in acute lymphoblastic leukemia / Inmunofenotipos aberrantes en la leucemia linfoblástica aguda

Abstract Acute lymphoblastic leukemia (ALL) is the most prevalent hematologic neoplasia worldwide. To classify leukemia, we analyzed the immunophenotypic characteristics in the neoplastic cells obtained with antibodies by cell flow cytometry or immunohistochemistry. The aberrant immunophenotypes are antigen expression patterns that differ from the normal hematopoietic maturation process, which can include some different lineage antigens such as myeloid antigens in ALL or asynchronous expression of antigens. These aberrant immunophenotypes have been studied as prognostic factors and residual disease markers. In this review, some aspects of aberrant immunophenotypes are addressed, including definition, epidemiology, and potential uses.

Resumen La leucemia linfoblástica aguda es la neoplasia hematológica más prevalente en el mundo. Para clasificar la leucemia se utilizan características inmunofenotípicas en las células neoplásicas que se pueden observar con anticuerpos en la citometría de flujo o mediante inmunohistoquímica. Los inmunofenotipos aberrantes son los patrones de expresión de los antígenos que difieren del proceso normal de maduración hematopoyética, y pueden incluir antígenos de linajes diferentes, como antígenos mieloides en la leucemia linfoblástica aguda, o la expresión asincrónica de antígenos. Estos inmunofenotipos aberrantes se han estudiado como factores de pronóstico y como marcadores de enfermedad mínima residual. En esta revisión se abordan algunos aspectos de los inmunofenotipos aberrantes, incluyendo su definición, epidemiología y usos potenciales.

Aberrant immunophenotypes in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most prevalent hematologic neoplasia worldwide. To classify leukemia, we analyzed the immunophenotypic characteristics in the neoplastic cells obtained with antibodies by cell flow cytometry or immunohistochemistry. The aberrant immunophenotypes are antigen expression patterns that differ from the normal hematopoietic maturation process, which can include some different lineage antigens such as myeloid antigens in ALL or asynchronous expression of antigens. These aberrant immunophenotypes have been studied as prognostic factors and residual disease markers. In this review, some aspects of aberrant immunophenotypes are addressed, including definition, epidemiology, and potential uses.

La leucemia linfoblástica aguda es la neoplasia hematológica más prevalente en el mundo. Para clasificar la leucemia se utilizan características inmunofenotípicas en las células neoplásicas que se pueden observar con anticuerpos en la citometría de flujo o mediante inmunohistoquímica. Los inmunofenotipos aberrantes son los patrones de expresión de los antígenos que difieren del proceso normal de maduración hematopoyética, y pueden incluir antígenos de linajes diferentes, como antígenos mieloides en la leucemia linfoblástica aguda, o la expresión asincrónica de antígenos. Estos inmunofenotipos aberrantes se han estudiado como factores de pronóstico y como marcadores de enfermedad mínima residual. En esta revisión se abordan algunos aspectos de los inmunofenotipos aberrantes, incluyendo su definición, epidemiología y usos potenciales.

The analysis of a group of acidic pharmaceuticals, carbamazepine, and potential endocrine disrupting compounds in wastewater irrigated soils by gas chromatography-mass spectrometry.

The analysis of pharmaceuticals and potential endocrine disruptors in the environment has rightly concentrated on their presence in wastewaters and possible contamination of receiving bodies, such as groundwaters. However, wastewater is increasingly being reused for irrigation and in order to fully understand the environmental fate of these compounds, reliable methods for their analysis in soil are required, of which there are relatively few available. This article reports a method for a range of acidic pharmaceuticals, carbamazepine, and endocrine disrupting compounds in soils with final analysis by gas chromatography-mass spectrometry. Two soil types (Phaeozom and Leptosol) and three fortification levels were used to validate the method. Recoveries of acidic pharmaceuticals varied between 62 and 102%, carbamazepine from 75 to 118%, and potential endocrine disruptors between 54 and 109%; most recoveries were between 75 and 95% and relative standard deviations were generally less than 10%. Detection limits were between 0.25 and 2.5 ng/g except for phthalates and 4-nonylphenols (25 ng/g). The method was used to analyze soils where untreated wastewaters have been used to irrigate crops for approximately 90 years. Concentrations of acidic pharmaceuticals in the soil were <1 ng/g and potential endocrine disruptors varied from below the limit of detection (estrone, 17beta-estradiol, and 17alpha-ethinylestradiol) to 2079 ng/L (bis-diethylhexyl phthalate). This data indicated that despite the continuous application of the contaminants over many years, concentrations were generally lower than those expected to be contributed by a single irrigation event. Only carbamazepine, at concentrations of 6.48 ng/g (in Phaeozem) and 5.14 ng/g (in Leptosol), showed any evidence of persistence in the soils analyzed.

Determination of acidic pharmaceuticals and potential endocrine disrupting compounds in wastewaters and spring waters by selective elution and analysis by gas chromatography-mass spectrometry.

Although the trend in development of analytical methods for emerging contaminants is towards reduced sample preparation and increased detector selectivity, there are still benefits from removal of matrix material during sample preparation. This paper describes a simple method for acidic pharmaceuticals and a range of potential endocrine disrupting compounds in untreated wastewaters and spring waters. It is based on separation of the two classes during elution from the extraction cartridge with final analysis by gas chromatography-mass spectrometry. 3,4-D was used as the recovery standard for the acids while 4-n-nonylphenol and [2H4]estrone were used for the endocrine disrupters; mean recoveries varied between 89% and 111%. The method was also extensively validated by fortification with the target compounds. Recoveries of acids were from 68% to 97% with relative standard deviations generally less than 10% and recoveries of endocrine disrupters were 68-109% with relative standard deviations less than 20%. Detection limits varied from 0.005 to 1 ng/L in spring water, and from 0.5 to 100 ng/L in untreated wastewater. Concentrations of the analytes in the wastewater ranged from 0.018 to 22.4 microg/L. Values were comparable to reported data, although concentrations were generally relatively high, probably because of a lack of treatment. Triclosan, phthalates, estrone, 17beta-estradiol, ibuprofen, and naproxen were present in the spring water from aquifers recharged indirectly with this wastewater after its use for irrigation; concentrations ranged from 0.01 to 25.0 ng/L. The much lower concentrations compared to wastewater indicate effective removal processes on passage through the soil and subsoil.

Reacción leucemoide monocítica asociada a tuberculosis ganglionar / Monocytic leukemoid reaction associated to tuberculosis lymphadenitis

En la reacción leucemoide (RL) un aumento importante en la cantidad de leucocitos, así como la presencia de células inmaduras en la sangre periférica, obligan al médico a descartar una leucemia aguda o crónica. Las RL pueden ser linfocíticas, granulocíticas, eosinofilicas y monocíticas, siendo estas últimas las más raras. Se informa el caso de una paciente de 64 años de edad con combe, PPD y anticuerpos antituberculosis positivos, así como leucocitosis y monocitosis persistente y linfadenitis granulomatosa en el reporte histopatológico de dos biopsias ganglionares, por lo que se concluye en una RL monocítica asociada a tuberculosis ganglionar, máxime que las alteraciones hematológicas y las adenomegalias desaparecieron con el tratamiento antifimico

Trombocitemia esencial infantil / Essential thrombocythemia in children

Introducción. La trombocitemia esencial (TE) es un síndrome mieloproliferativo poco frecuente caracterizado por una elevación importante de la cuenta plaquetaria, un incremento moderado de los leucocitos y anemia. Caso clínico. Escolar femenino de once años de edad con un cuadro de 45 días de evolución con cefalea, vómito, lipotimias y pérdida de peso. Diez días antes de su ingreso se agregó fiebre y dolor en hipocondrio derecho. A la exploración física: palidez y esplenomegalia. Por laboratorio trombocitosis persistente; el resto de exámenes incluyendo el cariotipo de la médula ósea, normales o negativos. Conclusiones. La TE es un diagnóstico al que se llega por exclusión. Se presenta la manera en que se llegó a este diagnóstico en nuestra paciente siendo este caso de TE infantil el primero reportado en México