Estudio Anatómico y Prevalencia del Canalis sinuosus Evaluado Mediante Cone Beam CT en Pacientes Chilenos / Anatomical Study and Prevalence of Canalis sinuosus Evaluated by Cone Beam CT in Chilean Patients

Canalis sinuosus, canal intraóseo localizado en región maxilar anterior, contiene elementos vasculonerviosos alveolares anterosuperiores. Diversas intervenciones en región maxilar anterior como colocación de implantes, exodoncias, instalación de microtornillos ortodóncicos, procedimientos quirúrgicos, entre otros, pueden comprometer al Canalis sinuosus y/o sus canales accesorios dañando los elementos contenidos en su interior causando complicaciones como hemorragias, parestesia, disestesia, etc. Dado el gran desconocimiento de su existencia, el Canalis sinuosus frecuentemente es confundido con lesiones patológicas y/o endodónticas. Clásicamente la literatura lo describe como una variación anatómica variación anatómica, sin embargo, presenta elevadas prevalencias (51,7 %-100 %), siendo cuestionada esta aseveración. Determinar prevalencia y característica s anatómicas del Canalis sinuosus mediante Cone Beam CT en pacientes chilenos del centro radiológico IMAPROX® entre 2017- 2021. Análisis retrospectivo de 220 CBCT maxilares anonimizados, considerando variables sexo, presencia del Canalis sinuosus, Canalis sinuosus uni/bilateral, diámetro mayor del Canalis sinuosus, presencia/número de accesorios. Análisis estadístico uni y bivariado. 100 % de prevalencia del Canalis sinuosus en ambos sexos, presencia bilateral 100 %. Diámetro mayor promedio del Canalis sinuosus: 2,58 mm. El 76,8 % presentó accesorios, siendo más prevalente la presencia de 2 CA (34,1 %). Una estructura anatómica normal habitual debe presentar sobre 50 % de prevalencia para ser considerada como tal, pero no hay consensos en criterios empleados para definir variación anatómica o estructura anatómica normal habitual. Literatura describe al Canalis sinuosus como variación anatómica, pero estudios actuales muestran elevadas prevalencias: Rusia 67 %, Brasil 88 %, Turquía, Colombia y Chile 100 %. Este estudio encontró 100 % de prevalencia, sugiriendo que Canalis sinuosus es una estructura anatómica normal habitual. Sin embargo, Canalis sinuosus es poco conocido asociándose a numerosas complicaciones por procedimientos odontológicos y/o quirúrgicos en RMA pudiendo generar hemorragias, parestesia/disestesia, dolor agudo, etc. Elevadas prevalencias reportadas sugieren que Canalis sinuosus es una estructura anatómica normal habitual y no una variación anatómica, pero se requieren más estudios y consensos para aseverarlo. Es de relevancia clínica conocer la existencia y localización del Canalis sinuosus para evitar complicaciones.

Canalis sinuosus, an intraosseous canal located in the anterior maxillary region, contains anterosuperior alveolar vascular-nervous elements. Various interventions in anterior maxillary region such as implant placement, extractions, installation of orthodontic microscrews, surgical procedures, among others, can compromise the Canalis sinuosus and/or its accessory canals, damaging the elements contained inside, causing complications such as bleeding, paresthesia, dysesthesia, etc. Given the great ignorance of its existence, Canalis sinuosus is frequently confused with pathological and/or endodontic lesions. Classically, the literature describes it as an anatomical variation, however, it presents high prevalence (51.7 %-100 %), this assertion being questioned. Objective: to determine the prevalence and anatomical characteristics of Canalis sinuosus using Cone Beam CT in Chilean patients from the IMAPROX® radiological center between 2017-2021. Retrospective analysis of 220 anonymous maxillary CBCT, considering variables sex, presence of Canalis sinuosus, uni/bilateral Canalis sinuosus, largest diameter of Canalis sinuosus, presence/number of accessory canals. Univariate and bivariate statistical analysis. The 100 % prevalence of Canalis sinuosus in both sexes, 100 % bilateral presence. Canalis sinuosus average major diameter: 2.58 mm, 76.8 % presented accessory canals, with the presence of 2 accessory canals being more prevalent (34.1 %). A habitual normal anatomical structure must have a prevalence of over 50 % to be considered as such, but there is no consensus on the criteria used to define anatomical variation or normal anatomical structure. Literature describes Canalis sinuosus as anatomical variation, but current studies show high prevalence: Russia 67 %, Brazil 88 %, Turkey, Colombia and Chile 100 %. This study found 100 % prevalence, suggesting that Canalis sinuosus is an normal anatomical structure. However, Canalis sinuosus is little known as it is associated with numerous complications from dental and/or surgical procedures in anterior maxillary region, which can cause bleeding, paresthesia/ dysesthesia, acute pain, etc. High reported prevalences suggest that Canalis sinuosus is an normal anatomical structure and not an anatomical variation, but more studies and consensus are required to confirm this. It is clinically relevant to know the existence and location of Canalis sinuosus to avoid complications.

Addition of plerixafor to G-CSF in poor mobilizing healthy related donors overcame mobilization failure: An observational case series on behalf of the Grupo Español de Trasplante Hematopoyético (GETH).

Plerixafor (Mozobil, Sanofi) is approved for using in patients with lymphoma and multiple myeloma when steady-state mobilization strategies fail. Although off-label use of plerixafor in healthy related donors (HRD) is known, limited data are available and no recommendations exist to guide its use in this setting. With the aim of collecting data from HRDs who received plerixafor in our country, we designed an observational case series study within the Spanish Group of Hematopoietic Transplant and Cell Therapy (GETH). Plerixafor was administered subcutaneously to 30 HRDs at a median dose of 0.24 mg/Kg (interquartile range (IQR): 0.23-0.25) because mobilization failure after using mobilization with G-CSF (mobilization failure was defined as collection of <4.0 × 106 CD34+ cells/Kg recipient). All HRDs received G-CSF at a median dose of 11 µg/Kg/day (IQR: 10-12) for 4-5 days. Leukocytapheresis after G-CSF mobilization was performed in 23 (77 %) HRDs collecting a median of 1.6 × 106 CD34+ cells/Kg recipient weight (IQR: 0.9-2.5). Addition of plerixafor allowed the collection of a higher median number of CD34 cells (4.98 × 106 CD34+ cells/Kg recipient weight (IQR: 3.5-5.8)) when compared with the collection of CD34+ cells with G-CSF alone (p < 0.01). The final median total number of CD34+ cells collected was 6.1 × 106/Kg recipient weight (IQR: 4.8-7.3). Mild adverse events related with plerixafor administration were reported in 8 (27 %) donors. In conclusion, addition of plerixafor after G-CSF mobilization failure in HRDs allowed collecting higher number of CD34+ cells in comparison with steady-state mobilization.

Proposal of a clinically relevant working classification of pituitary neuroendocrine tumors based on pituitary transcription factors.

The immunohistochemistry (IHC) characterization of pituitary transcription factors (PTFs) PIT1, TPIT, and SF1, which enable the identification of three different adenohypophyseal cell lines, has been incorporated into the latest classification system of the World Health Organization (WHO) for pituitary adenomas. This change overturns the concept of the adenoma as solely a hormone producer and classifies these tumors based on their cell lineage. The aim of the study was to provide a diagnostic algorithm, based on IHC expression of hypophyseal hormones with potential use in diagnostic practice, contributing to an improved classification of pituitary adenomas. Our sample included 146 pituitary adenomas previously classified based on hormonal subtypes by IHC (former 2004 WHO criteria) and re-evaluated after the IHC quantification of PIT1, TPIT, and SF1 expression, under WHO 2017 recommendations. We assessed the correlation between expression of PTFs and the classification as per hormonal IHC and correlated clinicopathological profiles based on PTFs. The IHC study of PTFs allowed reclassification of 82% of tumors that were negative for all pituitary hormones, with 21 positive cases for SF1 (reclassified as gonadotroph tumors), 1 positive case for TPIT (reclassified as a corticotroph tumor), and 4 positive cases for PIT1. Using SF1 enabled detection of a substantial portion of gonadotroph tumors, reducing the estimated prevalence of null cell tumors to less than 5%, and identification of plurihormonal pituitary neuroendocrine tumors with PIT1-SF1 coexpression and hormone-negative PIT1s, a group in which we did not observe differences in the clinical behavior compared with the rest of the tumors of the same cell lineage.Our results suggest that applying a diagnostic algorithm based on the study of PTFs could contribute to improving the classification of pituitary adenomas. By adding TPIT assessment, we propose a two-step algorithm, with hypophyseal hormones being used in a selective modality, depending on initial results.

Atypical pediatric presentation of lymphocytic thrombophilic arteritis: Diagnostic difficulties and recent nosological clarification.

A 4-year-old girl presented with a 2-month history of round, hypopigmented, slightly scaly patches measuring 1-6 cm and encircled by an erythematous halo, first appearing on the lower limbs then spreading to the whole body. Three biopsies were taken as the condition progressed, each showing a lymphocytic infiltrate affecting a medium-sized artery at the dermal-subcutaneous junction, with a concentric fibrin ring. These findings are characteristic of lymphocytic thrombophilic arteritis (LTA). The young age of our patient and the type of skin lesions she developed make this an atypical presentation of LTA, which usually manifests as hyperpigmented macules on the lower extremities, predominantly in dark-skinned women.

[Microglandular adenosis of the breast in a patient with a history of mediastinal radiotherapy]. / Adenosis microglandular mamaria en paciente con antecedente de radioterapia mediastínica.

The risk of secondary tumors in patients who have received mediastinal radiation therapy is well-known. Microglandular adenosis of the breast is a rare lesion that is considered benign, although its possible role as a precursor of invasive breast carcinoma has been considered. We present a case of microglandular adenosis in a patient who received mediastinal radiation therapy in childhood for Hodgkin's lymphoma. To our knowledge, this is the first reported case of microglandular adenosis in a patient with mediastinal radiotherapy which may shed light on its pathogenesis.

Mobilization of Hematopoietic Stem Cells into Peripheral Blood for Autologous Transplantation Seems Less Efficacious in Poor Mobilizers with the Use of a Biosimilar of Filgrastim and Plerixafor: A Retrospective Comparative Analysis.

INTRODUCTION: Biosimilars of granulocyte colony-stimulating factors (G-CSF) have shown similar efficacy to originator filgrastim (Neupogen® [NEU]; Amgen Inc.) as prophylaxis in neutropenia and in the mobilization of stem cells in patients receiving combination chemotherapy with G-CSF. METHODS: This was a retrospective study in which the characteristics of stem cell mobilization treated with a G-CSF alone were compared in 216 patients and 56 donors. The two G-CSF compared were NEU and the biosimilar filgrastim Zarzio® (Sandoz GmbH) (referred to hereafter as BIO). Primary objectives were mobilization rate (minimum of 10 × 103/ml CD34+ on day 4 of treatment [day +4]) and use of the immunostimulant plerixafor (PLEX) in each group. RESULTS: The general characteristics of the patients receiving NEU (n = 138) and those receiving BIO (n = 78) did not differ significantly. PLEX was used in 24% of BIO patients and in 25.7% of NEU patients. The median CD34+ cell count on day +4 was significantly lower in BIO patients who needed PLEX than in those who did not (2.4 vs. 4.8 × 103/ml; p = 0.002), as was the final CD34+ cell count (2.5 vs. 3.3 × 106/kg; p 0.03). Mobilization failure rate was higher in the BIO group than in the NEU group (20 vs. 0%; p = 0.01). With respect to donors, more than one apheresis was needed in three BIO donors, one of them with PLEX. The use of BIO was the only risk factor for mobilization failure in patients who needed PLEX (hazard ratio 10.3; 95% confidence interval 1.3-77.8). CONCLUSION: The study revealed that BIO had a lower efficacy for stem cell mobilization when the only treatment was G-CSF, especially in poor mobilizers needing PLEX.

Increased E2F1 mRNA and miR-17-5p Expression Is Correlated to Invasiveness and Proliferation of Pituitary Neuroendocrine Tumours.

miR-17-5p and E2F1 have been described as deregulated in cancer, but they have scarcely been studied in pituitary neuroendocrine tumours (PitNETs). This study evaluates the relationship of E2F1 and miR-17-5p with the invasiveness and proliferation of PitNETs. In this cross-sectional descriptive study, we evaluated the expression of E2F1, MYC, and miR-17-5p by quantitative real time PCR analysis in 60 PitNETs: 29 gonadotroph (GT), 15 functioning somatotroph (ST), and 16 corticotroph (CT) tumours, of which 8 were silent (sCT). The clinical data were collected from the Spanish Molecular Register of Pituitary Adenomas (REMAH) database. We defined invasiveness according to the Knosp classification and proliferation according to a molecular expression of Ki-67 ≥ 2.59. E2F1 was more expressed in invasive than in non-invasive tumours in the whole series (p = 0.004) and in STs (p = 0.01). In addition, it was overexpressed in the silent subtypes (GTs and sCTs; all macroadenomas) and normoexpressed in the functioning ones (fCTs and STs; some microadenomas). miR-17-5p was more expressed in proliferative than in non-proliferative tumours (p = 0.041) in the whole series but not by subtypes. Conclusions: Our study suggests that in PitNETs, E2F1 could be a good biomarker of invasiveness, and miR-17-5p of proliferation, helping the clinical management of these tumours.

Primary peritoneal clear cell carcinoma. A case report and literature review.

Primary peritoneal malignant tumors are exceptional. Among them, clear cell carcinoma is extremely rare, being only thirteen cases previously reported in the literature since 1990. We report a case of a 48-year-old Caucasian woman who was treated at the University General Hospital of Alicante. She consulted because of progressive abdominal pain over the last seven months, with the initial diagnosis of renal-ureteral colic. Ultrasound and computed tomography of the abdomen and pelvis revealed a 25 × 15 cm, well-defined cystic lesion with papillary projections, centrally located in the abdomen. The radiology report suggested a primary ovarian tumor versus peritoneal implant as the first option. The patient underwent an exploratory laparotomy showing a large cystic mass located in the urinary bladder peritoneum, firmly attached to the mesentery. The entire abdominal tumor was completely excised, and total hysterectomy with bilateral salpingo-oophorectomy and infra-colical omentectomy were performed. The final histological study revealed a new case of primary peritoneal clear cell carcinoma located in the urinary bladder peritoneum, firmly attached to the mesentery. Grossly, it was well-circumscribed and multicystic with papillary growth involving part of the inner wall. Microscopically, it showed tubulocystic and papillary patterns with highly atypical tumor cells. After an extensive immunohistochemical analysis, the most relevant finding was an ARID1A loss that was corroborated by molecular analysis showing an ARID1A deletion. The patient received systemic chemotherapy with carboplatin and paclitaxel protocol (Å ~ 4 cycles). Patient follow-up after the eighth month showed peritoneal implants predominantly in the right diaphragmatic cupule that were histologically confirmed as recurrence. She has just received another six cycles of chemotherapy with carboplatin and paclitaxel. Recognition of primary peritoneal clear cell carcinoma in this uncommon location, and exclude metastasis from the ovary, represents a diagnostic challenge.

How Valuable Is the RT-qPCR of Pituitary-Specific Transcription Factors for Identifying Pituitary Neuroendocrine Tumor Subtypes According to the New WHO 2017 Criteria?

The classification of pituitary neuroendocrine tumors (PitNETs) subtypes continues generating interest. In 2017, the World Health Organization (WHO) proposed considering the immunohistochemical (IHC) analysis of pituitary-specific transcription factors (TF) for their typification. The present study targeted the quantification of pituitary-specific TF (TPIT, PIT-1, SF-1, GATA2, ESR1) gene expression by RT-qPCR to overcome the shortcomings of IHC and to complement it. We analyzed 251 tumors from our collection of PitNETs and performed additional IHC studies in a subset of 56 samples to analyze the concordance between gene and protein expression of the TF. The molecular and IHC studies allowed us to significantly reduce the percentage of null cell tumors in our series, most of which were reclassified as gonadotroph tumors. The concordance between the molecular and the immunohistochemical studies was good for tumors coming from the corticotroph and Pit-1 lineages but worsened for the rest of the tumors. Indeed, the RT-qPCR helped to improve the typification of plurihormonal Pit-1 and unusual tumors. Overall, our results suggest that the RT-qPCR of pituitary-specific TF and hormone genes could help pathologists, endocrinologists, and neurosurgeons to improve the management of patients with pituitary tumors.

Medicines under additional monitoring in the European Union.

OBJECTIVE: The objective of this study was to analyse the characteristics of  medicines subject to additional monitoring. We assessed the following aspects:  the criteria applied to approve a medicine as being subject to additional  monitoring; the authorized dispensing conditions; the pharmacological groups to which they belong; and their post-authorisation safety. METHOD: We analysed the list published by the European Medicines Agency in  January 2017 (EMA/245297/2013 Rev.41). Information for the analysis was  obtained from the web sites of the European Medicines Agency and the Spanish  Agency of Medicines and Medical Devices. RESULTS: We assessed 316 medicines subject to additional monitoring. The most  common criterion used to assign a medicine as being subject to additional  monitoring was it being a new active substance (n = 197 [62.3%]). Other  common criteria were requiring a post-authorisation safety study (n = 52  [16.5%]) and being a biologic medicine but not a new active substance (n = 49  [15.5%]). Regarding dispensing conditions, nearly 66% of these medicines were authorized under restricted conditions. Until January 2017, the Spanish Agency  of Medicines and Medical Device published 14 safety reports related to medicines subject to additional monitoring. CONCLUSIONS: The group of medicines subject to additional monitoring mainly  includes new active substances. The most common pharmacological group is antineoplastic and immunomodulating agents. The postauthorisation safety  study has already produced information published by the Spanish Agency of  Medicines and Medical Devices.

Objetivo: El objetivo de nuestro estudio fue analizar las características de los  medicamentos sujetos a seguimiento adicional. Para ello, estudiamos: los  criterios aplicados para su designación, los criterios de dispensación autorizados,  los grupos farmacológicos a los que pertenecen y su seguridad postcomercialización.Método: Se analizó la lista publicada por la Agencia Europea de Medicamentos en enero de 2017 (EMA/245297/2013 Rev.41). La información para el análisis se extrajo de las páginas web de la Agencia Europea  de Medicamentos y la Agencia Española de Medicamentos y Productos  Sanitarios.Resultados: Se estudiaron 316 medicamentos sujetos a seguimiento adicional.  El criterio de designación más común fue ser un nuevo principio activo (n = 197  [62,3%]). Otros criterios de designación comunes fueron: requerir un estudio  postautorización de seguridad (n = 52 [16,5%]) y ser un medicamento  biológico, aunque no un nuevo principio activo (n = 49 [15,5%]). Con respecto a las condiciones de dispensación, casi el 66% de estos medicamentos se  autorizaron con criterios de dispensación restringidos. Hasta enero de 2017, la  Agencia Española de Medicamentos y Productos Sanitarios había publicado 14  notas informativas de seguridad referidas a los medicamentos sujetos a  seguimiento adicional.Conclusiones: Los medicamentos sujetos a seguimiento adicional incluyen mayoritariamente nuevas sustancias activas. El grupo farmacológico más frecuente es el de los fármacos antineoplásicos e  nmunomoduladores. La revisión postcomercialización de su seguridad ha  generado ya alguna información publicada por la Agencia Española de  Medicamentos y Productos Sanitarios.

Thawing of cryopreserved hematopoietic progenitor cells from apheresis with a new dry-warming device.

BACKGROUND: Current thawing techniques of cryopreserved progenitor cells are based on the use of a water bath. The aim of this study has been to assess the progenitor cell viability and the time of hematopoietic engraftment after transplantation of cell products thawed with a new dry-thawing device. STUDY DESIGN AND METHODS: In the preclinical phase, two cryobags from the same patient were thawed with the standard technique and with the dry system method in parallel (n=5, Protocol A and Protocol B, respectively). In the clinical phase, cryobags were thawed with the dry system and the time to hematopoietic engraftment after autologous transplantation (n=52) was compared with those of a control group of patients whose progenitor cell products were thawed with the standard technique (n=52). RESULTS: There were no statistical differences in nuclear and CD34+ cell viability, total colony-forming cells, and cloning efficiency after thawing with Protocols A and B. Days to neutrophil (>0.5×10(9) and >1×10(9) /L) and platelet engraftment (>20×10(9) and >50×10(9) /L) were not different between patients transplanted with products thawed with Protocols A and B. CONCLUSION: Progenitor cell viability and function are preserved with this dry-thawing system. The time to hematopoietic engraftment of patients after transplantation is comparable to those infused with progenitor cells thawed with the water bath technique. Thawing cell products without the use of water and in a dry environment might favor the use of this dry method.

Infecciones de las heridas quirúrgicas relacionadas a la atención perioperatoria / Surgical wound infections related to perioperative care

El presente estudio tuvo como objetivo conocer los factores de riesgo perioperatorios relacionados con las infecciones de heridas quirúrgicas en el quirófano. El instrumento a utilizar para valorar el proceso de atención perioperatoria fue diseñado por el grupo de investigación, fue aplicado a 30 pacientes que fueron sometidos a cualquier tipo de procedimiento quirúrgico. Los resultados obtenidos muestran que de los 30 pacientes estudiados se presentaron 6 casos de infección de la herida quirúrgica. El 33.33% de los pacientes presentaron inestabilidad en la temperatura corporal durante las fases del transoperatorio y el postoperatorio registrando valores inferiores a 36ºc; de igual manera la administración de profilaxis antibiótica se realizó al 66.67% de los pacientes. Al 66.7% de la muestra con infección en la herida quirúrgica no se les retiró el vello corporal, ya que no era necesario para la intervención, y el 33.33 % de la muestra restante fue depilada aunque no se realizó en un tiempo menor de dos horas por lo tanto es un factor de riesgo que incide en la infección de la herida quirúrgica.

The present study aimed to understand the risk factors related to perioperative surgical wound infections in surgery. The instrument used to evaluate the perioperative care process was designed by the research group, it was applied to 30 patients who were submitted to any type ofsurgical procedure. The results show that the 30 patients studied, there were six cases of surgical wound infection. 33.33% of the patients had unstable body temperature during the intraoperative phase and postoperative with values below 36 º c, in the same case the administration of antibiotic prophylaxis was performed at 66.67% of patients. At 66.7% of the sample with surgical wound infection were not body hair removal, because there was no necessary for intervention, and 33.33% of the remaining sample was shaved but not performed in a time less than two hours therefore. it is a risk factor that affects the surgical wound infection.

Análisis de variabilidad genética en Moniliophthora roreri con AP-PCR y RAPD en Antioquia, Colombia / Analysis of genetic variability in Moniliophthora roreri with AP-PCR and RAPD in Antioquia, Colombia

Moniliophthora roreri es el agente causante de la moniliasis del cacao, la enfermedad más severa en las plantaciones de cacao en el departamento de Antioquia, Colombia. Los marcadores moleculares RAPD (Random Amplyfied Polymorphism of DNA) y AP-PCR (Arbitraly Primed Polymerase Chain Reaction) fueron usados para estudiar la variabilidad genética de 170 aislamientos de M.roreri colectados en doce municipios de Antioquia. El análisis dividió la población en seis grupos,el grupo G1 fue el más grande y contenía el 95 por cien de los aislamientos con una alta similitud genética (coeficiente de similitud de 0,7 a 1), mientras los otros cinco grupos contenían solo aislamientos de Apartadó y Dabeiba con una similitud genética moderadamente baja (coeficiente de similitud entre 0,45 a 0,55). El análisis de componentes principales mostró una alta similitud genética entre la población excepto entre los aislamientos de Apartadó y Dabeiba, que registraron los más altos niveles de variabilidad genética con valores altos del índice de Shannon y el porcentaje de loci polimórficos, mientras los otros aislamientos registraron una baja variabilidad genética. Los valores de diversidad y diferenciación genética en la población muestran una introducción reciente de M.roreri en las plantaciones de cacao de Antioquia, y una reproducción predominantemente clonal en la población. De acuerdo con Amova, la mayoría de la variación genética se encontró dentro de los municipios (75,68 por cien) con solo un 5,94 por cien presente entre las subregiones.