PDGFRß promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin T cell lymphoma commonly driven by NPM-ALK. AP-1 transcription factors, cJUN and JUNb, act as downstream effectors of NPM-ALK and transcriptionally regulate PDGFRß. Blocking PDGFRß kinase activity with imatinib effectively reduces tumor burden and prolongs survival, although the downstream molecular mechanisms remain elusive. METHODS AND RESULTS: In a transgenic mouse model that mimics PDGFRß-driven human ALCL in vivo, we identify PDGFRß as a driver of aggressive tumor growth. Mechanistically, PDGFRß induces the pro-survival factor Bcl-xL and the growth-enhancing cytokine IL-10 via STAT5 activation. CRISPR/Cas9 deletion of both STAT5 gene products, STAT5A and STAT5B, results in the significant impairment of cell viability compared to deletion of STAT5A, STAT5B or STAT3 alone. Moreover, combined blockade of STAT3/5 activity with a selective SH2 domain inhibitor, AC-4-130, effectively obstructs tumor development in vivo. CONCLUSIONS: We therefore propose PDGFRß as a novel biomarker and introduce PDGFRß-STAT3/5 signaling as an important axis in aggressive ALCL. Furthermore, we suggest that inhibition of PDGFRß or STAT3/5 improve existing therapies for both previously untreated and relapsed/refractory ALK+ ALCL patients.

Safety of prasterone in breast cancer survivors treated with aromatase inhibitors: the VIBRA pilot study.

BACKGROUND: Due to safety concerns on estrogen-based treatments for genitourinary syndrome of menopause (GSM) in breast cancer survivors (BCS), new options are appearing, such as androgen-based treatments, which according to proprieties would not be transformed systemically to estrogens in patients receiving aromatase inhibitors (AIs). OBJECTIVE: The aim of this pilot study is to assess the security and efficacy of vaginal prasterone (dehydroepiandrostenedione [DHEA]) in BCS treated with AIs. METHODS: This open, prospective, pilot study included 10 BCS treated with AIs. All participants complained of severe GSM. DHEA was administrated as a vaginal ovule. Participants were instructed to use one ovule every night during the first month, and one ovule every two nights for the entire five remaining months. The patients were requested to attend seriated visits after the beginning of the prasterone treatment to evaluate symptoms, physical improvement and serum estradiol. RESULTS: Mean serum estradiol remained low from 3.4 pg/ml to 4.3 pg/ml (p = 0.9136) after 6 months of follow-up. The visual analog scale of dyspareunia improved from 8.5 to mean values after treatment of 0.4 (p = 0.0178). The Vaginal Health Index (VHI) scale and Female Sexual Function Index improved from 9.75 to 15.8 (p = 0.0277) and from an initial score of 11.2 to 20.6 (p = 0.0277), respectively. Vaginal pH changed from basal 8.1 to final 6.5 (p = 0.0330). CONCLUSION: Symptoms and physical examination regarding sexuality and vaginal health improved significantly, while serum estradiol remained at low levels. Prasterone seems a safe and effective option to treat GSM in BCS receiving AIs.

Radioactive and non-radioactive seeds as surgical localization method of non-palpable breast lesions.

The increasingly early diagnosis of breast disease and the more widespread use of primary systemic therapy leads to an increasing number of surgeries for non-palpable breast lesions (NPL) in clinical practice. Breast-conserving surgery often requires the use of an image-guided preoperative localization procedure, in which a device is placed within the lesion to be removed to guide the surgeon during surgery. These are patients with small, non-palpable tumors detected in the population screening mammogram, cases with significant reduction of the lesion after neoadjuvant chemotherapy and sometimes it is even necessary to mark axillary lymphadenopathies prior to systemic treatment. For decades, wire localization has been the standard for preoperative marking in breast cancer. Due to the external component of this device, extreme care must be taken not to alter its position before surgery, which is why it is placed hours before surgery and entails complex and limited flexibility in surgical programming. Intraoperative ultrasound improves this drawback but has the limitation that it can only be performed in those NPLs that have ultrasound translation. The Radioguided Occult Lesion Localization (ROLL) technique, although it is another alternative adopted by many institutions, is not without complications, among which the possibility of diffusion of the radiotracer into healthy tissue stands out. To overcome these problems, more recently, 125I radioactive seeds began to be used. Subsequently, thanks to technological advances, non-radioactive seed alternatives such as radar reflectors, magnetic seeds and radio frequency markers have emerged. These locating devices can be placed days before surgery, avoiding wire-related problems and complications. They are introduced percutaneously and identified intraoperatively using a detector device. There is no perfect intraoperative localization method for NPL excision, but fortunately, we have multiple techniques with different advantages and disadvantages that must be assessed and adapted to the center's own resources, the type of surgery, and always to the benefit of the patient.

[Moyamoya disease: revision and description of a number of pedriatic cases]. / Enfermedad de moyamoya: descripción de una serie de casos pediátricos.

INTRODUCTION: Moyamoya disease is caused because of progressive occlusion of the arterial circle of Willis, leading to a compensatory net-like abnormal vessels development. The objective is to describe the number of cases in our center (tertiary hospital). PATIENTS AND METHODS: Retrospective study. Revision of pediatric medical histories diagnosed of moyamoya disease or moyamoya syndrome (in case of predisposing disease) between 2005 and 2018. Demographic variables were collected, related to diagnosis, risk factors, treatment, and follow-up. RESULTS: Seven cases were collected with a median age of 6 years and an equitable distribution by sex. Five associated predisposing pathologies (Down syndrome, neurofibromatosis, sickle cell disease, Behcet). The main clinical diagnosis was neurological focus (five cases), followed by epileptic seizures (four), and headache (two). One was asymptomatic at diagnosis. Six strokes were documented, five of them were isquemic. The arteriography (goldstardard) was made in five patients. Five presented bilateral involvement of the vessels, the internal carotid arteries and the middle cerebral arteries were the most affected. Six received acetylsalicylic acid treatment and five of them required antiepileptic drugs. Revascularization surgery (encephaloduroarteriomyosinangiosis) was performed in four patients, and in one, strokes persisted. The most prevalent sequelae were hemiparesis and psychomotor retardation. CONCLUSIONS: The risk factors presented in our patients match to those described in the literature. The symptoms at the onset can be diverse and ischemic strokes predominate in our series. Revascularization surgery was effective in more than half of the cases. Subsequent follow-up is necessary to assess complications and sequelae.

TITLE: Enfermedad de moyamoya: descripción de una serie de casos pediátricos.Introducción. La enfermedad de moyamoya se produce por la oclusión de las arterias alrededor del polígono de Willis y genera una amplia red de vasos colaterales. El objetivo es describir la serie histórica de nuestro centro (hospital terciario). Pacientes y métodos. Es un estudio retrospectivo. Se hizo una revisión de historias clínicas de pacientes pediátricos diagnosticados de enfermedad o síndrome de moyamoya (si patología predisponente) entre 2005 y 2018. Se recogieron variables demográficas, relacionadas con el diagnóstico, factores de riesgo, tratamiento y seguimiento. Resultados. Se obtuvieron siete casos, con una mediana de edad de seis años y distribución por sexos equitativa. Cinco asociaban patologías predisponentes (síndrome de Down, neurofibromatosis, drepanocitosis y Behçet). La clínica predominante en el diagnóstico fue focalidad neurológica (cinco casos), seguida de crisis epilépticas (cuatro) y cefalea (dos). Un paciente era asintomático en el momento del diagnóstico. Se documentaron seis ictus, cinco de los cuales fueron isquémicos. La arteriografía (técnica de referencia) constaba en cinco pacientes. Cinco presentaban afectación bilateral y estaban mayormente afectadas las arterias carótidas internas y las cerebrales medias. Seis recibieron tratamiento con ácido acetilsalicílico y cinco necesitaron fármacos antiepilépticos. La cirugía de revascularización (encefaloduroarteriomiosinangiosis) se realizó en cuatro pacientes y en uno persistieron los ictus. Las secuelas más prevalentes fueron hemiparesia y retraso psicomotor. Conclusiones. Los factores de riesgo presentados en nuestros pacientes se ajustan a los descritos en la bibliografía. La clínica en el inicio puede ser diversa y predominan los ictus isquémicos en nuestra serie. La cirugía de revascularización fue efectiva en más de la mitad de los casos. Es necesario un seguimiento posterior para evaluar complicaciones y secuelas.

Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.

PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.

Multiparametric MR imaging to assess response following neoadjuvant systemic treatment in various breast cancer subtypes: Comparison between different definitions of pathologic complete response.

OBJECTIVES: To validate the performance of multiparametric magnetic resonance (MR) imaging to assess pathologic response to neoadjuvant systemic therapy (NST) in various breast cancer subtypes considering two definitions of pCR: absence of any residual invasive cancer or DCIS (ypT0) and absence of invasive tumour cells (ypT0/is). METHODS: Institutional review board-approved retrospective study, with waiver of the need to obtain informed consent. From January 2015 to June 2017, 81 women with 82 breast cancers undergoing NST were included. Eighteen lesions (22%) were immunohistochemically HER2-positive, 12 (15%) triple negative (TN), 42 (51%) luminal B-like and 10 (12%) luminal B-like/HER2-positive. Breast MR imaging was performed before and after NST. A comparative analysis considering pCR as ypT0 and ypT0/is was carried out. Performance of univariate and multivariate models to potentially predict pathologic response were evaluated. RESULTS: ypT0 was attained in 23% (19/82) of cases and ypT0/is in 33% (27/82) of cases. In both scenarios, HER2-positive subtype achieved the best response, 53% and 48%, respectively. A significant relationship was found between late enhancement and pathologic response (p < 0.001) regardless of pCR definition. In the ypT0 scenario, mean ADC ratio in the pCR subgroup was significantly higher than that in the non-pCR subgroup (p = 0.021) but no significant relationship was noted in ypT0/is. A multivariate model including MR late enhancement, ADC ratio and tumor subtype identified pathologic response with 86% and 84% accuracy when ypT0 and ypT0/is were considered, respectively. CONCLUSION: MR imaging late enhancement and ADC ratio along with breast cancer IHC subtype identify pathologic response following NST with high accuracy, achieving the highest NPV in TN and HER2-positive tumors and the highest PPV in luminal B-like subtypes, regardless of the definition of pCR as ypT0 or ypT0/is. In light of these findings and given that residual DCIS does not have an impact on survival rates, ypT0/is seems to be the preferable definition of pCR.

Comparison of the analytical and clinical performance of five tests for the detection of human papillomavirus genital infection.

HPV-based screening provides greater protection against cervical cancer (CC) than cytology-based strategies. Currently, several molecular diagnostic assays for the detection of human papillomavirus (HPV) are available. In this study, we analyzed 5 different HPV testing and genotyping techniques (Hybrid Capture 2 [HC2; Qiagen, Hilden, Germany], AnyplexTMII HPV28 [Anyplex; Seegene, Seoul, Korea], Linear Array [Roche, Branchburg, NJ, USA], GP5+/6+ PCR-EIA-RH [Labo Bio-medical Products, Rijswijk, The Netherlands] and CLART2 [Genomica, Madrid, Spain]) in 295 women referred to the hospital Colposcopy Clinic from 2007 to 2008 due to positive HPV test results or an abnormal Pap test. DNA extraction for HPV genotyping was performed in cervical sample specimens after Pap test and HPV detection by HC2. The inclusion criteria were: (1) adequate cervical sampling with sufficient material for the Pap test and HPV detection and genotyping, and (2) colposcopically-directed biopsy and/or endocervical curettage. HC2 showed the highest sensitivity for high-grade squamous intraepithelial lesion and CC (HSIL+) detection (96.1%), but all the HPV genotyping tests showed a higher specificity. (Anyplex 86.8%; Linear Array 86.0%; GP5+/6+ 78.8%; CLART2 76.5%). The agreement between HC2 results and the other techniques was similar: 82.4%, kappa=0.650 for Anyplex; 83.4%, kappa=0.670 for Linear Array, 79.93%, kappa=0.609 for GP5+/6+ and 82.4%, kappa=0.654 for CLART2. HPV 16 and/or 18 infection was a risk factor for underlying HSIL+ in the univariate analysis. Anyplex showed the highest risk of underlying HSIL+ after positive HPV 16 and/or 18 tests (OR 31.1; 95% CI 12.1-80.0).

Factores de riesgo cardiovascular en estudiantes de enfermería de una universidad pública / Cardiovascular risk factors among nursing students of a public university / Fatores de risco cardiovascular em estudantes de enfermagem de uma universidade pública

Introducción: Los factores de riesgo cardiovascular son aquellos signos biológicos y hábitos adquiridos identificados en la población general; por tanto, los jóvenes estudiantes no están exentos a presentarlos. Objetivo: Identificar la presencia de factores de riesgo cardiovascular en estudiantes de la licenciatura en enfermería de una universidad pública del estado de Oaxaca. Metodología: Estudio descriptivo, transversal, realizado en la licenciatura en enfermería. La muestra obtenida fue de 286 seleccionados por un muestreo aleatorio simple. Los datos se recabaron con la cédula de factores de riesgo cardiovascular en jóvenes universitarios. Resultados: Los jóvenes universitarios tienen antecedentes familiares ligados a factores de riesgo cardiovascular: 45.8% de hipertensión, 43.4% de hipercolesterolemia y 39.8% de diabetes; el 55.9% realizan actividad física leve; el 60.1% rara vez o nunca consumen bebidas gaseosas; el 51.8% solo realizan una o dos comidas al día. Discusión y conclusión: El factor heredofamiliar con mayor prevalencia fue la hipertensión arterial; otros factores identificados fueron la inactividad física, las dietas inadecuadas y el ayuno prolongado. Es relevante propiciar que los participantes mejoren su calidad de vida durante su estancia universitaria para disminuir la evolución de estos factores de riesgo y desarrollar estrategias conducentes a la reducción de estos, como un autocuidado responsable, expresado en una dieta sana y la práctica de ejercicio físico regular.

Introduction: Cardiovascular risk factors are diverse biological signs and acquired habits which the general population can have; and therefore young students are not exempt of them. Objective: To identify the presence of cardiovascular risk factors among baccalaureate-level nursing students of a public university in the state of Oaxaca, Mexico. Methodology: This is a descriptive and transversal study. The sample of 286 individuals was constituted by simple random sampling. Data were recorded in specific risk factors charts. Results: Some of these university students have familial backgrounds which could be linked to cardiovascular risks: 45.8% hypertension; 43.4% hypercholesterolemia, and 39.8% diabetes. Also related, 55.9% perform mild physical activity; 60.1% rarely or never consume carbonated beverages, and 51.8% have only one or two meals a day. Discussion and conclusion: The most prevalent familial risk factor was arterial hypertension; while other identified risk factors were physical inactivity, inadequate diets, and prolonged fasting. It is relevant to encourage young university students to improve their lifestyles in order to lower their cardiovascular risk factors. Among the addressing strategies can be a responsible self-care reflected by healthy diets and physical activity in an ongoing basis.

Introdução: Os fatores de risco cardiovascular são aqueles signos biológicos e hábitos adquiridos que se identificam na população geral; portanto, os jovens estudantes não estão isentos de apresentá-los. Objetivo: Identificar a presencia de fatores de risco cardiovascular em estudantes da licenciatura em enfermagem de uma universidade pública do estado de Oaxaca. Metodologia: Estudo descritivo, transversal, realizou-se na licenciatura em enfermagem, a amostra obtida foi de 286 selecionados em uma amostragem aleatória simples. Os dados coletaram-se com a cédula de fatores de risco cardiovascular em jovens universitários. Resultados: Os jovens universitários têm antecedentes familiares relacionados com fatores de risco cardiovascular: 45.8% de hipertensão, 43.4% de hipercolesterolemia e 39.8% de diabetes, 55.9% realiza atividade física leve, 60.1% alguma vez ou nunca consome bebidas gasificadas, só 51.8% realiza uma ou duas refeições ao dia. Discussão e conclusão: O fator hereditário com maior prevalência foi a hipertensão arterial, os fatores identificados foram a inatividade física, as dietas inadequadas e o jejum prolongado. É relevante propiciar que os participantes melhorem sua qualidade de vida durante sua estadia universitária, para diminuir a evolução destes fatores de risco, e desenvolver estratégias que conduzam à redução dos mesmos como um autocuidado responsável, expressado em uma dieta saudável e a prática do exercício físico regular.

Aortic Graft Mycotic Pseudoaneurysm as a Severe Complication After Multivisceral Transplantation: A Case Report.

BACKGROUND: Surgical complications in multivisceral transplantation (MVT) are frequent and always severe. Those related to technical issues are relevant as they have implications not only on the graft but also on patient survival. The aim of this study was to review our case-based data and experience with 5 MVT performed since December 2004. CASE REPORT: A 38 year-old woman presented with ultra-short bowel syndrome due to massive ischemia also affecting the celiac trunk. She also had moderate to severe hepatitis/steatosis with some degree of fibrosis on liver biopsy, due to long-term home parenteral nutrition (HPN). An MVT was carried out in September 2010 including the liver, stomach, pancreatoduodenal complex with the spleen, and small bowel. The postoperative course was complicated by a leak from the pyloromiotomy, requiring reoperation on postoperative day 13. She also had central line catheter infection and renal impairment, requiring renal replacement therapy, and was discharged on postoperative day 150. Fifteen days later she was hospitalized because of severe abdominal pain associated with an abdominal mass. Computed tomography showed an aortic donor graft pseudoaneurysm, so we decided to operate on the patient. A complete resection of the pseudoaneurysm using an interposed polytetrafluoroethylene graft was performed. Six months after the MVT, the patient died due to sepsis, despite a functional graft and complete digestive autonomy. CONCLUSIONS: Although this complication is rare, surgical complications in MVT are severe and may seriously impair graft and patient survival.

Surgical technique for en bloc transurethral resection of bladder tumour with a Hybrid Knife(®). / Técnica quirúrgica de la resección transuretral de tumor vesical en bloque con Hybrid Knife(®).

BACKGROUND: Bladder cancer is the second most common malignancy of the urinary tract and the 9th worldwide. Latin American has an incidence of 5.6 per 100,000 inhabitants per year. Seventy-five percent of newly diagnosed cases are nonmuscle invasive bladder cancer, and 25% of cases present as muscle invasive. The mainstay of treatment for nonmuscle invasive bladder cancer is loop transurethral resection. In 2013, the group led by Dr Mundhenk of the University Hospital of Tübingen, Germany, was the first to describe the Hybrid Knife(®) equipment for performing en bloc bladder tumour resection, with favourable functional and oncological results. OBJECTIVE: To describe the surgical technique of en bloc bladder tumour resection with a Hybrid Knife(®) as an alternative treatment for nonmuscle invasive bladder tumours. MATERIAL AND METHODS: A male patient was diagnosed by urotomography and urethrocystoscopy with a bladder tumour measuring 2×1cm on the floor. En bloc transurethral resection of the bladder tumour was performed with a Hybrid Knife(®). RESULTS: Surgery was performed for 35min, with 70 watts for cutting and 50 watts for coagulation, resecting and evacuating en bloc the bladder tumour, which macroscopically included the muscle layer of the bladder. There were no complications. CONCLUSION: The technique of en bloc bladder tumour resection with Hybrid Knife(®) is an effective alternative to bipolar loop transurethral resection. Resection with a Hybrid Knife(®) is a procedure with little bleeding and good surgical vision and minimises the risk of bladder perforation and tumour implants. The procedure facilitates determining the positivity of the neoplastic process, vascular infiltration and bladder muscle invasion in the histopathology study.

Mind the model for end-stage liver disease: model for end-stage liver disease score as an indicator of hemoderivate transfusion and survival in liver transplantation.

The scarcity of liver donors has increased the necessity to closely select recipients to improve liver transplantation outcomes. If we were able to recognize those recipients with the best outcomes, then this could result in a better and more accurate selection of our donors. Hemoderivate transfusion is one of the main important factors to analyse. We reviewed the data of all of our liver transplant recipients from May 1998 to December 2013 and selected 888 patients with complete records. We divided these patients into 5 groups to get a better selection. We found differences between these groups with respect to the following: recipient age at the time of transplantation, percentage of patients with hepatocarcinoma, and those with hepatitis C virus (HCV)-related etiology. Also, intensive care unit (ICU) time and the need for retransplantation were distinctive factors with observable differences between our groups. With respect to model for end-stage liver disease (MELD) score, the groups were clearly defined by their mean MELD score, finding significant statistical differences between these groups with respect to this score. We also found a significant relationship between MELD scores and survival in the different groups. This is also the first review in which the MELD score and intraoperative transfusion requirements are well associated with patient and graft survival.

[Presence of intramammary lymph nodes in the preoperative lymphoscintigraphy to locate the sentinel lymph node. Clinical significance]. / Presencia de ganglios intramamarios en la linfogammagrafía prequirúrgica para localizar el ganglio centinela. Relevancia clínica.

OBJECTIVE: The routes of lymphatic drainage from a breast cancer are the axilla (the most frequent) and the extra axillary regions. Among the latter, there are the so-called intrammamary lymph nodes (IMLN). This study has aimed to assess the incidence of IMLNs in our patients and study the evolution of these cases with IMLN in the lymphoscintigraphy. MATERIAL AND METHODS: Thirty-eight patients (out of 1725) with IMLN in the pre-operative lymphoscintigraphy were assessed. During the surgical procedure, using a gamma probe, IMLNs were located and excised. After their harvesting, a meticulous surgical field scan was performed. When the axillary sentinel node was positive for metastasis, a complete axillary lymphadenectomy was performed. In those where the axillary sentinel node was negative and IMLN was positive (IMLN+), axillary lymphadenectomy was also performed, except for one case. RESULTS: Thirty-four out of the 38 IMLNs were obtained (89.5%), because no lymphatic tissue was found in pathology analysis in three cases (8%) and in one patient (3%) IMLN was not found during surgery. Ten (26%) metastatic IMLNs were located and the remaining 24 IMLNs cases (63%) were metastasis-free. During the clinical follow-up, one patient with IMLN+ developed hepatic metastases. The remaining 33 patients did not present any recurrence. No follow-up data were available for three patients. CONCLUSIONS: IMLN and axillary sentinel node biopsy are recommended when both are depicted in preoperative lymphoscintigraphy. The axilla treatment will only depend on the axillary sentinel node status. Based on the data from other authors and our own experience, avoiding the axillary lymphadenectomy when a metastatic IMLN without axillary involvement seems reasonable.

Histologic evaluation of organ preservation injury and correlation with cold ischemia time in 13 intestinal grafts.

Lesions produced in the graft mucosa due to harvesting, storage, and implantation must be graduated to assess the subsequent protocolized biopsy specimens. The aim is to identify type and intensity of graft mucosal lesions observed immediately after implantation. Congestion, hemorrhage, microthrombi, neutrophilic infiltrates, shortening of villi, epithelial detachment, erosion, and crypt loss were separately evaluated by two pathologists in mucosal biopsy specimens from 13 grafts. Each change was assessed as normal, mild, moderate, or severe and by splintering the summation of points a global score was designed. Cold ischemia time was registered. Correlation between the pathologists' evaluations and between final preservation injury degree and cold ischemia time was determined using the "index of correlation rho (ρ)" (Spearman's test). The same changes were assessed in 19 biopsy specimens from day 2 to day 6 (3.6 ± 1.1) to determine their evolution. Congestion was found in 7 biopsy specimens, microthrombi in 2, hemorrhage in 4, neutrophils in 6, villous atrophy in 8, epithelial detachment in 9, erosions in 2 and/or crypt loss in 2. The maximum degree of preservation injury was expressed as intense congestion and hemorrhage associated with epithelial detachment and villous atrophy. The global preservation score was grade 3 in 2 cases, grade 2 in 5, grade 1 in 2, and grade 0 in 4. There was positive correlation (ρ = 0.915) in the evaluation between pathologists (P < .01), total agreement in 9 biopsy specimens, and partial agreement (only 1 point disagreement) in 4. Mean cold ischemia time was 327 ± 101 min. (135-480). There was positive correlation (ρ = 0.694) between preservation score and cold ischemia time (P < .01). In the follow-up biopsy procedures, histological injury decreased by at least one grade in every case. Additionally, karyorrhexis was observed in 3 grafts and very occasional apoptosis in 2 others. This scale achieves good reproducibility and allows graduate preservation injury in intestinal transplantation.

Histologic evaluation of post-implantation immediate C4d deposition in 13 intestinal grafts: correlation with cell-based crossmatching, cold ischemia time, and preservation injury.

C4d deposits are predictive of humoral rejection in kidney and heart transplantation. The aim of this study was to identify C4d deposit patterns in intestinal mucosa of the grafts on biopsy specimens obtained immediately after implantation and to detect if it could be a valuable tool to predict humoral or acute rejection. A second objective was to search for a statistically significant relationship between positive C4d deposition and other collected variables. Thirteen immediately post-transplantation mucosal graft biopsy specimens, formalin fixed, underwent immunohistochemical stain for C4d deposits. Diffuse intense staining of capillary endothelium was considered positive and absent, focal or weak stains as negative. Preservation injury grade and cold ischemia times were registered for each case. Donor-specific preformed antibodies were detected by complement dependent cytotoxicity serologic technique (crossmatching). Another 19 endoscopic follow-up biopsy specimens from days 2 to 6 were also evaluated. Statistical studies were made using the index of correlation ρ (Spearman's test). Diffuse intense C4d deposits were observed in 2 grafts, focal and weak in 5, and completely negative in 6. The mean cold ischemia time was 327 ± 101 minutes. Two cases showed diffuse positive deposits, 1 had a positive crossmatch and the cold ischemia time was 360 minutes whereas the other had not preformed antibodies and its cold ischemia time was 475 minutes. Humoral or acute rejection was not observed in follow-up mucosal biopsy specimens. There was no statistically significant relationship between the C4d deposition, cold ischemia time, crossmatching results, and preservation injury degree. In conclusion, C4d deposition was not a helpful tool for diagnosis of humoral rejection and prediction of acute rejection during the early post-transplantation period.

Renal failure associated with intestinal transplantation: our experience in Spain.

BACKGROUND: Renal failure (RF) is a frequent complication in non-renal solid organ transplants. In the present study, we analyze our experience with intestinal transplants (ITx). METHODS: Between 2004 and 2012, we performed 21 ITx in 19 adult patients. Alemtuzumab was used as an induction agent followed by tacrolimus. Renal function was assessed before ITx and during the perioperative period. RESULTS: The main cause for transplants was non-resectable desmoids tumors (33.3%), followed by vascular thrombosis (19%) and others. Medical complications were frequent, especially infectious diseases, which were the most common (51%). Surgical complications were also frequent, but most of them (>50%) were mild but leading to a great number of re-operations and prolonged stays in hospital. Acute rejection is very frequent (66.6%) but mild in more than 70% of the cases. Finally, RF was very frequent (68.4%; 13/19 patients) and accounted for 15.6% of all medical complications. Causes were multiple. One patient is awaiting a kidney transplant, but no other patients need renal replacement therapy at the moment. Ileostomy closure was performed in 5 of 12 patients alive, showing improved renal function in 3 of them. CONCLUSIONS: RF is a problem in ITx and is always multifactorial. Increases in hospital stay, higher morbidity and is a cause for hospital readmission. Almost all patients had an impaired renal function when discharged. Immunosuppressants and ileostomy closure as soon as possible might prevent RF.

The treatment for primary immune thrombocytopenia with romiplostim in adult and paediatric patients: use experience at a Spanish university hospital.

WHAT IS KNOWN AND OBJECTIVE: Primary immune thrombocytopenia (ITP) is characterized by accelerated platelet destruction, as well as suboptimal platelet production. Thrombopoietin (TPO) receptor agonists bind to and activate human TPO receptor, and have been shown to increase platelet counts. In this study, we assessed the effectiveness and safety of long-term administration of TPO agonist romiplostim in adult and paediatric patients. METHODS: This is a retrospective observational study that included every ITP patient (adults and children) who received romiplostim since its inclusion in our institutional formulary. Data on patients' demographics, romiplostim doses, platelet counts, use of rescue medication and concurrent therapies were collected. Outcomes for effectiveness evaluation were proportion of patients who achieved a platelet response (platelet count >50 × 10(9) per litre and double the platelet count at baseline on any scheduled visit, excluding counts obtained within 8 weeks after receipt of rescue medications), proportion of patients who achieved a durable response (platelet responses during 6 or more weeks of the last 8 weeks of treatment), proportion of patients needing rescue medication, proportion of patients able to stop or reduce concurrent treatment and mean number of weekly platelet responses. Safety was assessed on the basis of the incidence of adverse events documented on the patients' medical records. RESULTS AND DISCUSSION: This study enrolled ten adults and four paediatric patients. None of the paediatric patients and one adult patient had been splenectomized (contraindicated in the other adults). In the adult population, eight achieved a response at least once during treatment, and 1 achieved a durable response. Four patients needed rescue medication (mostly intravenous immunoglobulins). Three patients were able to stop concurrent ITP therapies, and the mean number of weekly platelet responses was 6. All four paediatric patients achieved a response at least once during treatment, and three achieved durable responses. Three patients needed rescue medication. The only patient who was receiving concurrent ITP medication was able to stop it, and the mean number of weekly platelet responses was 25. No serious adverse events were registered during treatment in either population. WHAT IS NEW AND CONCLUSION: The effectiveness of romiplostim was variable with few adult patients achieving a durable response. Our paediatric patients responded better with most achieving a durable response. The treatment was safe for both groups of patients. Studies should be conducted to identify patients more likely to benefit from this treatment.

The impact of human papillomavirus genotype on colposcopic appearance: a cross-sectional analysis.

OBJECTIVE: To study colposcopic performance in diagnosing high-grade cervical intraepithelial neoplasia or cervical cancer (CIN2+ and CIN3+) using colposcopic characteristics and high-risk human papillomavirus (hrHPV) genotyping. DESIGN: Cross-sectional multicentre study. SETTING: Two colposcopy clinics in The Netherlands and Spain. POPULATION: Six hundred and ten women aged 17 years and older referred for colposcopy because of abnormal cytology. METHODS: A cervical smear was obtained. Colposcopists identified the worst lesion, graded their impression and scored the colposcopic characteristics of the lesions. Up to four biopsies were collected, including one biopsy from visually normal tissue. MAIN OUTCOME MEASURES: CIN2+ and CIN3+, positive for HPV16 or other high-risk HPV types (non-16 hrHPV-positive). RESULTS: The mean age in HPV16-positive CIN2+ women was 35.1 years compared with 39.1 years in women with other hrHPV types (P = 0.002). Sensitivity for colposcopy to detect CIN2+ was 87.9% (95%CI 83.2-91.5), using colposcopic cut-off of 'any abnormality'. The remaining CIN2+ were found by a biopsy from visually normal tissue or endocervical curettage (ECC). Detection of CIN2+ by lesion-targeted biopsies was not different between HPV16-positive women [119/135; 88.1% (95%CI 81.2-92.9)] and non-16 hrHPV-positive women [100/115; 87.0% (95%CI 79.1-92.3); P = 0.776]. In multivariate analysis, 'acetowhitening' [odds ratio (OR) 1.91, 95%CI 1.56-3.17], 'time of appearance' (OR 1.95, 95%CI 1.21-3.15) and 'lesion >25% of visible cervix' (OR 2.25, 95%CI 1.44-3.51) were associated with CIN2+. CONCLUSIONS: In this population following European screening practice, HPV16-related CIN2+ lesions were detected at younger age and showed similar colposcopic impression as non-16 hrHPV high-grade lesions. There was no relationship between any of the colposcopic characteristics and HPV16 status.

[Acute visual loss in pregnancy caused by craniopharyngioma]. / Pérdida visual aguda en el embarazo causada por craneofaringioma.

CASE REPORT: A 38-year-old female, at 20-weeks gestation, experienced a sudden visual loss and visual-field abnormalities. The neuroimaging tests showed a craniopharyngioma. Surgical removal was performed with a successful outcome as regards the pregnancy and visual function. DISCUSSION: It is known that pituitary adenomas may grow during pregnancy; however this is unusual in craniopharyngiomas. They usually present with visual problems due to their suprasellar topography. Surgery is the treatment of choice, the outcome essentially depending on its complete resection.

Clinical evaluation of high-risk HPV detection on self-samples using the indicating FTA-elute solid-carrier cartridge.

BACKGROUND: High-risk human papillomavirus (hrHPV) testing in cervical screening is usually performed on physician-taken cervical smears in liquid-based medium. However, solid-state specimen carriers allow easy, non-hazardous storage and transportation and might be suitable for self-collection by non-responders in screening and in low-resource settings. OBJECTIVES: We evaluated the adequacy of self-collected cervicovaginal (c/v) samples using a Viba-brush stored on an Indicating FTA-elute cartridge (FTA-based self-sampling) for hrHPV testing in women referred to a gynecology clinic due to an abnormal smear. STUDY DESIGN: 182 women accepted to self-collect a c/v sample. After self-sampling, a physician obtained a conventional liquid-based cervical smear. Finally, women were examined by colposcopy and a biopsy was taken when clinically indicated. Self-samples required only simple DNA elution, and DNA was extracted from physician-obtained samples. Both samples were tested for 14 hrHPVs by GP5+/6+-EIA-LQ Test and SPF(10)-DEIA-LiPA(25). RESULTS: Both assays detected significantly more hrHPV in physician-collected specimens than in self-collected samples (75.3% and 67.6% by SPF(10); 63.3% and 53.3% by GP5+/6+, respectively). The combination of physician-collected specimen and GP5+/6+ testing demonstrated the optimal balance in sensitivity (98.0%) and specificity (48.1%) for CIN2+ detection in this referral population. A test system of FTA-based self-collection and SPF(10) hrHPV detection approached this sensitivity (95.9%) and specificity (42.9%). CONCLUSIONS: These results show that the clinical performance of hrHPV detection is determined by both the sample collection system and the test method. FTA-based self-collection with SPF(10) testing might be valuable when a liquid-based medium cannot be used, but requires further investigation in screening populations.