GRANULOCYTE AND MONOCYTE ADSORPTIVE APHERESIS (GMA) IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A USEFUL THERAPEUTIC TOOL NOT JUST IN ULCERATIVE COLITIS BUT ALSO IN CROHN´S DISEASE.

INTRODUCTION: Granulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn´s disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission. PATIENTS AND METHOD: Retrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions. RESULTS: We treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory-or-intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD. CONCLUSIONS: GMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory-or-intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.

Resultados clínicos de artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar / Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study

Objetivos: Resultados clínicos, radiológicos y funcionales de la primera serie española de pacientes intervenidos de artroplastia total de cadera (ATC) asistida mediante brazo robótico Mako® (Stryker) del Hospital Clínico San Carlos (HCSC) de Madrid. Material y métodos: Estudio descriptivo prospectivo que analiza los primeros 25 pacientes intervenidos de ATC asistida por robot (ATCaR) en el HCSC, con un seguimiento mínimo de 4meses. Se evaluaron la demografía, los estudios de imagen (procesamiento Mako®, Rx y TAC), los parámetros clínicos, la funcionalidad (Harris modificada) y las complicaciones asociadas. Resultados: La edad media fue 67,2años (min 47, max 88), siendo el 56% varones. El 88% corresponden a coxartrosis primaria, el 4% postraumática, el 4% secundaria a NAV y el 4% secundaria a choque femoroacetabular. El tiempo medio de cirugía fue de 116,9minutos (min 92, max 150). La media de las cinco primeras intervenciones fue 122,6minutos, y la de las cinco últimas, de 108,2minutos. Como complicaciones intraoperatorias se cuantificaron 4 pérdidas de marcadores intraoperatorios. El tiempo de ingreso medio fue 4,4días (min 3, max 7), con una disminución de hemoglobina posquirúrgica media de 3,08±1,08g/dl, requiriendo transfusión en el 12% de los casos. Se registran tres complicaciones médicas durante el ingreso, destacando un síndrome confusional con caída y fractura periprotésica AG1 no desplazada. El análisis del posicionamiento de los implantes registrados con sistema Mako® fueron 40,55±1,53 grados de inclinación y 12,2±3,6 grados de anteversión acetabular. El estudio de imagen posquirúrgico realizado a los pacientes, en concordancia con Mako®, muestra valores de inclinación acetabular de 41,2±1,7 en Rx y versión acetabular de 16±4,6 en TAC. La discrepancia de longitud de cadera varía de valores preoperatorios de −3,91mm (DE: 3,9; min −12, max 3) a 1,29mm (DE: 1,96) tras la cirugía registrados con Mako...(AU)

Objectives: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. Material and methods: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. Results: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min −12, max 3) to 1.29mm (SD: 1.96) after surgery registered with...(AU)

[Translated article] Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study / Resultados clínicos de la artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar

Objetivos: Resultados clínicos, radiológicos y funcionales de la primera serie española de pacientes intervenidos de artroplastia total de cadera (ATC) asistida mediante brazo robótico Mako® (Stryker) del Hospital Clínico San Carlos (HCSC) de Madrid. Material y métodos: Estudio descriptivo prospectivo que analiza los primeros 25 pacientes intervenidos de ATC asistida por robot (ATCaR) en el HCSC, con un seguimiento mínimo de 4meses. Se evaluaron la demografía, los estudios de imagen (procesamiento Mako®, Rx y TAC), los parámetros clínicos, la funcionalidad (Harris modificada) y las complicaciones asociadas. Resultados: La edad media fue 67,2años (min 47, max 88), siendo el 56% varones. El 88% corresponden a coxartrosis primaria, el 4% postraumática, el 4% secundaria a NAV y el 4% secundaria a choque femoroacetabular. El tiempo medio de cirugía fue de 116,9minutos (min 92, max 150). La media de las cinco primeras intervenciones fue 122,6minutos, y la de las cinco últimas, de 108,2minutos. Como complicaciones intraoperatorias se cuantificaron 4 pérdidas de marcadores intraoperatorios. El tiempo de ingreso medio fue 4,4días (min 3, max 7), con una disminución de hemoglobina posquirúrgica media de 3,08±1,08g/dl, requiriendo transfusión en el 12% de los casos. Se registran tres complicaciones médicas durante el ingreso, destacando un síndrome confusional con caída y fractura periprotésica AG1 no desplazada. El análisis del posicionamiento de los implantes registrados con sistema Mako® fueron 40,55±1,53 grados de inclinación y 12,2±3,6 grados de anteversión acetabular. El estudio de imagen posquirúrgico realizado a los pacientes, en concordancia con Mako®, muestra valores de inclinación acetabular de 41,2±1,7 en Rx y versión acetabular de 16±4,6 en TAC. La discrepancia de longitud de cadera varía de valores preoperatorios de −3,91mm (DE: 3,9; min −12, max 3) a 1,29mm (DE: 1,96) tras la cirugía registrados con Mako...(AU)

Objectives: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. Material and methods: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. Results: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min −12, max 3) to 1.29mm (SD: 1.96) after surgery registered with...(AU)

[Translated article] Validation of the Spanish version of the modified Harris score / Validación de la versión española de la escala de Harris modificada

Objetivos: Resultados clínicos, radiológicos y funcionales de la primera serie española de pacientes intervenidos de artroplastia total de cadera (ATC) asistida mediante brazo robótico Mako® (Stryker) del Hospital Clínico San Carlos (HCSC) de Madrid. Material y métodos: Estudio descriptivo prospectivo que analiza los primeros 25 pacientes intervenidos de ATC asistida por robot (ATCaR) en el HCSC, con un seguimiento mínimo de 4meses. Se evaluaron la demografía, los estudios de imagen (procesamiento Mako®, Rx y TAC), los parámetros clínicos, la funcionalidad (Harris modificada) y las complicaciones asociadas. Resultados: La edad media fue 67,2años (min 47, max 88), siendo el 56% varones. El 88% corresponden a coxartrosis primaria, el 4% postraumática, el 4% secundaria a NAV y el 4% secundaria a choque femoroacetabular. El tiempo medio de cirugía fue de 116,9minutos (min 92, max 150). La media de las cinco primeras intervenciones fue 122,6minutos, y la de las cinco últimas, de 108,2minutos. Como complicaciones intraoperatorias se cuantificaron 4 pérdidas de marcadores intraoperatorios. El tiempo de ingreso medio fue 4,4días (min 3, max 7), con una disminución de hemoglobina posquirúrgica media de 3,08±1,08g/dl, requiriendo transfusión en el 12% de los casos. Se registran tres complicaciones médicas durante el ingreso, destacando un síndrome confusional con caída y fractura periprotésica AG1 no desplazada. El análisis del posicionamiento de los implantes registrados con sistema Mako® fueron 40,55±1,53 grados de inclinación y 12,2±3,6 grados de anteversión acetabular. El estudio de imagen posquirúrgico realizado a los pacientes, en concordancia con Mako®, muestra valores de inclinación acetabular de 41,2±1,7 en Rx y versión acetabular de 16±4,6 en TAC. La discrepancia de longitud de cadera varía de valores preoperatorios de −3,91mm (DE: 3,9; min −12, max 3) a 1,29mm (DE: 1,96) tras la cirugía registrados con Mako...(AU)

Objectives: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. Material and methods: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. Results: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min −12, max 3) to 1.29mm (SD: 1.96) after surgery registered with...(AU)

[Translated article] Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4 months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2 years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative haemoglobin decrease of 3.08±1.08g/dl, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4 months). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study. / Resultados clínicos de artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4month). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

Somatic structural variant formation is guided by and influences genome architecture.

The occurrence and formation of genomic structural variants (SVs) is known to be influenced by the 3D chromatin architecture, but the extent and magnitude have been challenging to study. Here, we apply Hi-C to study chromatin organization before and after induction of chromothripsis in human cells. We use Hi-C to manually assemble the derivative chromosomes following the occurrence of massive complex rearrangements, which allows us to study the sources of SV formation and their consequences on gene regulation. We observe an action-reaction interplay whereby the 3D chromatin architecture directly impacts the location and formation of SVs. In turn, the SVs reshape the chromatin organization to alter the local topologies, replication timing, and gene regulation in cis We show that SVs have a strong tendency to occur between similar chromatin compartments and replication timing regions. Moreover, we find that SVs frequently occur at 3D loop anchors, that SVs can cause a switch in chromatin compartments and replication timing, and that this is a major source of SV-mediated effects on nearby gene expression changes. Finally, we provide evidence for a general mechanistic bias of the 3D chromatin on SV occurrence using data from more than 2700 patient-derived cancer genomes.

Papiloflebitis como manifestación de poliarteritis nodosa / Papillophlebitis as manifestation of polyarteritis nodosa

Varón de 35 años de edad diagnosticado de poliarteritis nodosa que desarrolló una papiloflebitis de su ojo izquierdo. Presentó en su evolución edema macular que fue tratado con inyecciones intravítreas de aflibercept con buena evolución posterior y recuperación completa de la agudeza visual. En el curso de su enfermedad presentó también epiescleritis del ojo adelfo. La papiloflebitis consiste en una oclusión de la vena central de la retina no isquémica de origen inflamatorio. La poliarteritis nodosa es una vasculitis necrotizante sistémica caracterizada por la afectación de arterias musculares de pequeño y mediano calibre. La afectación ocular se produce en el 10-20% de los casos y típicamente afecta a las arterias coroideas. La afectación venosa es extremadamente rara y si se produce suele ser por extensión de la inflamación adyacente

A 35 year-old-man diagnosed with polyarteritis nodosa developed papillophlebitis on his left eye. Throughout the evolution of the disease, he had a macular oedema treated with intravitreal injections of aflibercept, with adequate recovery of visual acuity. He also had episcleritis on the other eye. Papillophlebitis is a non-ischaemic central retinal vein occlusion of inflammatory cause. Polyarteritis nodosa is a systemic necrotising vasculitis characterised by lesions of small and medium sized arteries. Ocular involvement occurs in 10-20% of patients, and typically affects the choroidal arteries. Only arteries are usually affected, but in very rare cases adjacent veins may be involved due to the adjacent inflammation

Tension subcutaneous haematomas associated with anticoagulants in the elderly: Do they have earlier morbidity and mortality than hip fractures? / Hematomas subcutáneos a tensión por anticoagulantes en ancianos: ¿más morbimortalidad precoz que las fracturas de cadera?

INTRODUCTION: Complications related to anticoagulant therapy have been widely described, although tension haematomas in the extremities are frequently undervalued, and commonly considered banal pathologies. MATERIAL AND METHOD: Retrospective descriptive study between 2014 and 2017, including patients with limb haematomas after minimal trauma related with anticoagulant therapy, and surgically treated by Traumatology. RESULTS: 32 cases were eventually included, 81% were women, average age of 83.56 years, and a mean aCCI of 5.97. Anatomical location of haematomas was 65.6% in leg/foot, 15.6% in thigh/buttock, and 18.8% in the upper limb. Seventy-eight point thirteen percent received acenocoumarol, 15.63% LMWH, and 3.13% NOACs. Of the cases, 59.38% were due to AF, 15.63% to valvular heart disease/valve prosthesis, and 12.5% to PE/DVT. The mean time from diagnosis to surgical drainage was 2.66 days, mainly as a result of alterations in coagulation parameters. Forty-six point eighty-eight percent were reoperated for new drainage, cure or skin defect coverage, and 3 patients required embolisation. Of the patients, 78% needed consultation with other specialties. The average length of stay was 22.34 days, and the in-hospital mortality rate was 9.38%. CONCLUSION: Tension haematomas in the extremities associated with anticoagulants occur in patients with multiple comorbidities that make them vulnerable. Surgical drainage is usually delayed by numerous factors which lead to skin defects that require further surgical operations, and prolonged hospital stays that are associated with medical complications. In our study, the average length of stay and in-hospital mortality rate were higher than those for hip fractures, so we should not underestimate this pathology.

Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation.

Global loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to megabases. However, the distribution of PMDs within and between tumor types, and their effects on key functional genomic elements including CGIs are poorly defined. We comprehensively show that loss of methylation in PMDs occurs in a large fraction of the genome and represents the prime source of DNA methylation variation. PMDs are hypervariable in methylation level, size and distribution, and display elevated mutation rates. They impose intermediate DNA methylation levels incognizant of functional genomic elements including CGIs, underpinning a CGI methylator phenotype (CIMP). Repression effects on tumor suppressor genes are negligible as they are generally excluded from PMDs. The genomic distribution of PMDs reports tissue-of-origin and may represent tissue-specific silent regions which tolerate instability at the epigenetic, transcriptomic and genetic level.

Papillophlebitis as manifestation of polyarteritis nodosa. / Papiloflebitis como manifestación de poliarteritis nodosa.

A 35 year-old-man diagnosed with polyarteritis nodosa developed papillophlebitis on his left eye. Throughout the evolution of the disease, he had a macular oedema treated with intravitreal injections of aflibercept, with adequate recovery of visual acuity. He also had episcleritis on the other eye. Papillophlebitis is a non-ischaemic central retinal vein occlusion of inflammatory cause. Polyarteritis nodosa is a systemic necrotising vasculitis characterised by lesions of small and medium sized arteries. Ocular involvement occurs in 10-20% of patients, and typically affects the choroidal arteries. Only arteries are usually affected, but in very rare cases adjacent veins may be involved due to the adjacent inflammation.

The circular RNome of primary breast cancer.

Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (R < 0.2) correlation with the expression level of the linear gene. In silico analysis showed only a minority (8.5%) of circRNAs could be explained by known splicing events. Both these observations suggest that specific regulatory processes for circRNAs exist. We confirmed the presence of circRNAs of CNOT2, CREBBP, and RERE in an independent pool of primary breast cancers. We identified circRNA profiles associated with subgroups of breast cancers and with biological and clinical features, such as amount of tumor lymphocytic infiltrate and proliferation index. siRNA-mediated knockdown of circCNOT2 was shown to significantly reduce viability of the breast cancer cell lines MCF-7 and BT-474, further underlining the biological relevance of circRNAs. Furthermore, we found that circular, and not linear, CNOT2 levels are predictive for progression-free survival time to aromatase inhibitor (AI) therapy in advanced breast cancer patients, and found that circCNOT2 is detectable in cell-free RNA from plasma. We showed that circRNAs are abundantly present, show characteristics of being specifically regulated, are associated with clinical and biological properties, and thus are relevant in breast cancer.

Author Correction: Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

In the Methods section of this Article, 'greater than' should have been 'less than' in the sentence 'Putative regions of clustered rearrangements were identified as having an average inter-rearrangement distance that was at least 10 times greater than the whole-genome average for the individual sample. '. The Article has not been corrected.

Chemical acetylation of nixtamalized maize flour and structural, rheological and physicochemical properties of flour, dough and tortillas.

Nixtamalized maize tortilla is a basic food for the Mexican population. It has high energy due to high starch, which may be modified to decrease its bioavailability and to produce changes in the characteristics of flours. For this research, nixtamalized maize flour was prepared and subjected to an acetylation chemical process, with and without prior hydrolysis. Raw maize flour, traditionally nixtamalized maize flour, acetylated-nixtamalized maize flour (AF) and acetylated-hydrolyzed nixtamalized maize flour (AHF) were prepared and evaluated. These flours were used for dough and tortilla preparation and analyzed for degree of substitution (DS), physicochemical properties, structure, thermal, rheological, morphological and texture properties. FTIR spectra and DS showed the presence of acetyl groups. AHF showed the highest value for water absorption index. The resistant starch increased 0.27 and 0.42% for AF and AHF samples. The gelatinization enthalpy (∆Hg) for AF was greater than other flours. AF tortillas showed better characteristics than the traditional ones and their consumption was recommended since showed better RS.

Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration.

A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.

Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

Cardiopatías congénitas y embarazo / Congenital heart disease and pregnancy

Las cardiopatías congénitas han ido aumentando entre las mujeres embarazadas de los países desarrollados debido a su mayor supervivencia, la tardía edad gestacional, las nuevas técnicas de fecundación y el aumento de los factores de riesgo cardiovascular. Los cambios fisiológicos del embarazo, parto y posparto conllevan un incremento en el volumen plasmático, la frecuencia cardiaca, el gasto cardiaco y un descenso de las resistencias vasculares periféricas. Aunque bien tolerados en las pacientes con corazones estructuralmente sanos, estos cambios pueden conllevar un mayor riesgo de morbimortalidad materno fetal entre pacientes con cardiopatía. De ahí que conocer la fisiopatología del embarazo, los fármacos que pueden ser utilizados, el riesgo de transmisión de la cardiopatía materna al feto o las cardiopatías congénitas que conllevan un mayor riesgo obstétrico resulte fundamental a la hora de realizar una adecuada valoración, seguimiento y tratamiento de la cardiópata gestante

Congenital heart disease has increased among pregnant women from developed countries due to their longer survival, later age at pregnancy, new fertilization techniques and increased cardiovascular risk factors. The physiological changes of pregnancy, childbirth and postpartum increase plasma volume, heart rate, and cardiac output and decrease peripheral vascular resistance. Although these changes are well tolerated in patients with structurally healthy hearts, these changes may lead to a greater risk of fetal and maternal morbidity and mortality among patients with heart disease. Therefore, knowledge of the pathophysiology of pregnancy, the drugs that can be used, the risk of maternal transmission of disease to the fetus, and of the congenital heart diseases that pose an increased obstetric risk is essential for the proper assessment, monitoring and treatment of pregnant women with heart disease