Expression of Programmed Death Ligand 1 in Breast Cancer in Mexican Women.

Background: Breast cancer is one of the most common malignant forms of neoplasia worldwide; programmed death protein 1 (PD-1), an inhibitory receptor of T lymphocytes, and its ligand programmed death ligand 1 (PD-L1), play an important role in the ability of tumor cells to evade the host's immune system. Methods: We conducted a descriptive, observational study using retrospective data and an open evaluation using immunohistochemistry to determine the general prevalence of PD-L1 expression in 63 women with breast cancer who underwent a modified radical mastectomy, or quadrantectomy, with axillary lymph node removal. Results: The prevalence of PD-L1 expression was 32% in patients with breast cancer treated with radical mastectomy. PD-L1 expression was higher in patients with large tumor size (19% for pT1, 37% for pT2, 50% for pT3, and 100% for pT4), metastasis in regional lymph nodes (25% for N0, 38% for N1, 75% for pN2, and 38% for pN3), and higher histological grade carcinoma (0% for grade 1, 23% for grade 2, and 50% for grade 3). Conclusions: These findings suggest that PD-L1 expression is heterogeneous in breast cancer tumors and that its expression varies highly in tumor regions over time. The evaluation of PD-L1 expression is significant, because of the therapeutical implications that could improve the outcomes and prognosis of these patients.

Neuroendocrine Tumor of the Common Bile Duct: Case Report.

Carcinoma of the extrahepatic biliary tract accounts for <2% of all cancers. Neuroendocrine tumor of the extrahepatic bile duct is very rare, and there are <200 cases reported since 1959. The preoperative diagnosis is infrequent (5.12%). The definite diagnosis relies on postoperative pathology which utilized immunohistochemistry study on many biomarkers to diagnose the histological subtypes of neuroendocrine neoplasms, such as chromogranin A, synaptophysin, and neuron-specific enolase. When the primary tumor has no metastases, radical removal of the lesion appears as curative treatment. The treatment of the carcinoid syndrome or other functioning syndrome is the first priority. We report a case of a 12-year-old Mexican woman with neuroendocrine tumor of the extrahepatic bile duct (common bile duct neuroendocrine tumor) seen in our hospital. Resection of the common bile duct, cholecystectomy, end to side Roux-en-y hepaticojejunostomy, and portal lymphadenectomy was performed. A review of the pertinent literature was performed. Given the rarity of the disease, treatment principles are based mainly on retrospective series and case reports. We present the eighth case in adolescence in the literature.

Covid 19: manifestaciones neurológicas / COVID-19: Neurological manifestations

RESUMEN La enfermedad por coronavirus 2019 (covid-19) puede ser clasificada en asintomática, leve, moderada, grave y crítica de acuerdo con los síntomas respiratorios. En 36% de los casos pueden presentarse manifestaciones en el sistema nervioso central, periférico y musculoesquelético. En algunos países el acceso a la unidad de cuidados intensivos ha sido limitado, generado dilemas éticos.

SUMMARY: Coronavirus disease 2019 (COVID-19) can be classified as asymptomatic, mild, moderate, severe, and critical according to respiratory symptoms. Thirty-six percent of its manifestations can be neurological either central, peripheral or musculoskeletal. In many countries, access to intensive care units and ventilatory devices has been limited, generating ethical dilemmas.

Covid-19 y epilepsia / COVID-19 and epilepsy

RESUMEN La encefalopatía es una manifestación neurológica frecuente en los pacientes en UCI con Covid-19. Es importante realizar un adecuado diagnóstico diferencial con el estado epiléptico no convulsivo, para poder optimizar su cuidado y pronóstico. El uso del video-electroencefalograma (VEEG) bajo adecuadas normas de bioseguridad, permite realizar un adecuado diagnóstico del estado epiléptico, disminuyendo el numero de ingresos innecesarios a la Unidad de Cuidado Intensivo, y el tiempo de sedación con anestésicos. La telemedicina para los pacientes con epilepsia ha demostrado ser una herramienta útil, al no mostrar inferioridad en comparación con las visitas cara a cara habituales en términos de diferencia significativa en el número de las crisis, hospitalizaciones, visitas a la sala de emergencias o cumplimiento de medicamentos.

SUMMARY: Encephalopathy is a frequent neurological manifestation in ICU patients with COVID-19. It is important to make an accurate differential diagnosis with non-convulsive epileptic status, in order to optimize the management and prognosis. The use of Video-EEG monitoring assuring biosecurity standards, allows an adequate diagnosis of epileptic status, reducing the number of unnecessary admissions to the intensive care unit, sedation time and anesthetics use. The use of telemedicine in patients with epilepsy has proven to be a useful tool, compared to standard outpatient visits in terms of number of seizures, admissions, emergency visits, or adherence to the medication.

Impact of the Type of Analgesic Therapy on Postsurgical Complications of Patients with Kidney Cancer Undergoing Nephrectomy.

BACKGROUND: The treatment of kidney cancer usually involves surgery, and in some cases systemic therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to control postsurgical pain in patients undergoing nephrectomy for renal cancer. Nevertheless, the association between these drugs and adverse postsurgical outcomes, including deterioration of renal function, is not fully established. METHODS: This retrospective cohort study included patients >18 years old with kidney cancer undergoing nephrectomy between January 2006 and January 2018. The primary endpoint was to determine the impact of postsurgical analgesic therapy (NSAIDs vs. acetaminophen) on renal function and postsurgical complications. This study was approved by our scientific and bioethical committee. RESULTS: One hundred patients were included in the final analysis. Clear-cell renal-cell carcinoma was the most frequent histologic subtype. Adequate acute pain control was accomplished in 91% of the patients during hospitalization. Twenty percent of the patients presented postsurgical complications. Bleeding-related complications were the most frequent (9%), followed by surgical-site infection (6%) and acute renal injury (6%). The administration of NSAIDs was not related to any postsurgical complication in comparison with the use of acetaminophen (21.3 vs. 17.9%, respectively). The length of hospital stay did not differ between patients treated with NSAIDs and those treated with acetaminophen (the average stay was 4 days for both groups, p = 0.32). CONCLUSION: The use of NSAIDs was not related to acute kidney injury, postsurgical complications, or prolonged hospital stay in patients with renal cancer undergoing nephrectomy.

Tratamiento del estado epiléptico, consenso de expertos. Asociación Colombiana de Neurología, Comité de Epilepsia / Treatment of status epilepticus, an expert consensus report. Colombian Neurology Association - Epilepsy Committee

RESUMEN INTRODUCCIÓN: El estado epiléptico (EE) es una condición ocasionada por la falla en los mecanismos de supresión de las crisis epilépticas. Se considera como una urgencia neurológica y obliga al profesional de la salud a conocer las características de presentación para poder estabilizar al paciente. La mortalidad varía entre el 2 % y el 50 % según el grupo etario. OBJETIVO: Construir una serie de sugerencias para el tratamiento del EE, como resultado del consenso por común acuerdo de expertos en epilepsia, teniendo en cuenta el contexto colombiano. MÉTODOS: Se llevó a cabo un consenso formal de expertos con 16 neurólogos-epileptólogos de adultos y niños. Las preguntas y sugerencias fueron revisadas en dos fases, donde fueron calificadas y consensuadas por los participantes. RESULTADOS: Se evaluaron 15 preguntas, con sus respectivas sugerencias sobre el manejo del estado epiléptico, se tuvieron en cuenta referencias bibliográficas relevantes consideradas por los expertos y de acuerdo con el contexto colombiano. CONCLUSIONES: Los resultados de este consenso presentan una serie de sugerencias para el tratamiento del estado epiléptico tanto en los primeros niveles de atención como en los de alta complejidad para mejorar el pronóstico del paciente, de acuerdo con el contexto colombiano.

SUMMARY INTRODUCTION: Status epilepticus is a condition caused by failure in the mechanisms of suppression of epileptic seizures. It is considered a neurological emergency, and mortality varies between 2 % to 50 % according to the age group. Due to the above, it is relevant that health professionals know the characteristics of SE in order to stabilize the patient. OBJECTIVE: To define a series of propositions for the treatment of SE, as a result of consensus by common agreement of experts in epilepsy, taking into account the Colombian context. METHODS: A formal consensus of experts was carried out with 16 adult and pediatric neurologists-epilep-tologists. The questions and propositions were reviewed in two phases, where they were graded and agreed by the participants. RESULTS: Fifteen questions were evaluated on the management of status epilepticus. Relevant bibliographic references were considered by the experts according to the Colombian context. CONCLUSIONS: As results of this consensus we present a series of propositions for the treatment of status epilepticus for the primary level of care and high complexity level of care in order to improve the patient's prognosis, according to the Colombian context.

Spontaneous regression as a 'burned-out' non-seminomatous testicular germ cell tumor: a case report and literature review.

Testicular germ cell tumors (TGCTs) are the most frequent type of cancer in young adults. An exceptional event is the spontaneous regression (SR) of the primary tumor. Herein, we describe a burned-out non-seminomatous TGCT case and relevant literature review. A 34-year-old male presenting with low back pain was found to have a retroperitoneal mass upon urotomography. During workup, a heterogeneous testicular mass was evident, and its biopsy showed findings that support the diagnosis of spontaneous tumoral regression. The patient underwent unilateral orchiectomy and a chemotherapy protocol was later initiated, with 85% regression of the retroperitoneal metastatic mass. No progression of the primary tumor has been found. The etiology of SR across different cancer types appears to be associated with the host's immune response and an angiogenic disturbance of the tumor microenvironment. The burned-out phenomenon is a rare event that needs further research into its molecular sequencing.

A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility.

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.

Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility.

OBJECTIVE: The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). PATIENTS AND METHODS: The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. RESULTS: We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively). CONCLUSIONS: These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor.

INTRODUCTION: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. METHODS: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. RESULTS: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. CONCLUSIONS: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.

Influence of the IL6 gene in susceptibility to systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. METHODS: We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan(®) allele discrimination technology. RESULTS: Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). CONCLUSION: Our results suggest that the IL6 gene may influence the development of SSc and its progression.

A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis.

INTRODUCTION: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. METHODS: A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. RESULTS: Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). CONCLUSION: Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis.

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort.

OBJECTIVES: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. METHODS: A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. RESULTS: A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). CONCLUSIONS: The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.

[Relationship between reticulated platelets and megacaryocyte number in thrombocytopenic patients]. / Relación entre plaquetas reticuladas y número de megacariocitos en pacientes con trombocitopenia.

BACKGROUND AND INTRODUCTION: Marrow aspiration is a test that helps the pathogenic diagnosis of thrombocytopenia. Our goal was to analyze the correlation between reticulated platelets (RP) values in peripheral blood with megakaryocytic number in bone marrow in a group of thrombocytopenic patients. PATIENTS AND METHODS: Prospective observational study in thrombocytopenic patients, between June 2002 and June 2005. RP determination was performed by flow cytometry using whole blood. We used a monoclonal anti-glycoprotein-IIIa antibody (CD61PerCP) for platelet identification and orange thiazole (Retic-count) as platelet mRNA stain. Marrow study was conducted by marrow aspiration. RESULTS: RP were measured in 54 thrombocytopenic patients with bone marrow study. Three were excluded from the study. Thirty-two patients had central thrombocytopenia with diminished megakaryocytes (MK) and/or dysplasia, mean of RP 9.5% (CI 95%:5.6%-13.4%). Thirteen patients had high MK,mean of RP 25.7%(CI 95%:13.1%-38.3%). Six patients had normal MK, mean of RP 13.6% (CI 95%:0.6%-26.8%). There were differences between the group of increased MK and the group of central thrombocytopenias (p=0001). A value of RP>or=11% showed a sensitivity of 70% and specificity of 81% for the diagnosis of marrow aspirate with increased MK. CONCLUSIONS: RP are an indirect marker of megakaryocyte number in bone marrow. A value of RP>or=11% in patients with thrombocytopenia, especially with an acute onset, would indicate regenerative thrombocytopenia, while in the presence of low levels of RP a marrow aspiration should be performed.

Relación entre plaquetas reticuladas y número de megacariocitos en pacientes con trombocitopenia / Relationship between reticulated platelets and megacaryocyte number in thrombocytopenic patients

Fundamento y objetivo: El aspirado medular es un test de gran valor para el diagnóstico patogénico de las trombocitopenias. El objetivo fue analizar la correlación entre los valores de plaquetas reticuladas (PR) en sangre periférica con el número de megacariocitos en médula ósea en un grupo de pacientes con trombocitopenia. Pacientes y método: Estudio prospectivo observacional en pacientes con trombocitopenia entre junio de 2002 y junio de 2005. La determinación de PR se realizó mediante citometría de flujo con el uso de sangre total. Se utilizó un anticuerpo monoclonal anti-glucoproteína-IIIa (CD61 PerCP®) para la identificación de plaquetas y naranja de tiazol (Retic-count®) para la tinción del ácido ribonucleico plaquetario residual. El estudio medular se realizó mediante aspirado medular. Resultados: Se determinaron las PR en 54 pacientes con trombocitopenia que tenían estudio medular. Tres pacientes se excluyeron del estudio. Treinta y dos pacientes tenían trombocitopenias centrales con megacariocitos disminuidos o displasia, con una media de PR del 9,5% (intervalo de confianza [IC] del 95%: del 5,6 al 13,4%). Trece pacientes tenían megacariocitos elevados, con una media de PR del 25,7% (IC del 95%: del 13,1 al 38,3%). Seis pacientes tenían megacariocitos normales, con una media de PR del 13,6% (IC del 95%: del 0,6 al 26,8%). Se observaron diferencias entre el grupo con megacariocitos aumentados y el grupo de trombocitopenias centrales (p=0,001). Un valor de PR superior o igual al 11% mostró sensibilidad del 70% y especificidad del 81% para el diagnóstico de aspirado medular con megacariocitos aumentados. Conclusiones: Las PR son un marcador indirecto de la producción de megacariocitos en médula ósea. La presencia de PR superior o igual al 11% en pacientes con trombocitopenia, especialmente de inicio agudo, indicaría trombocitopenia regenerativa, mientras que ante la presencia de valores bajos de PR sería recomendable realizar un aspirado medular (AU)

Background and Introduction: Marrow aspiration is a test that helps the pathogenic diagnosis of thrombocytopenia. Our goal was to analyze the correlation between reticulated platelets (RP) values in peripheral blood with megakaryocytic number in bone marrow in a group of thrombocytopenic patients. Patients and methods: Prospective observational study in thrombocytopenic patients, between June 2002 and June 2005. RP determination was performed by flow cytometry using whole blood. We used a monoclonal anti-glycoprotein-IIIa antibody (CD61PerCP) for platelet identification and orange thiazole (Retic-count®) as platelet mRNA stain. Marrow study was conducted by marrow aspiration. Results: RP were measured in 54 thrombocytopenic patients with bone marrow study. Three were excluded from the study. Thirty-two patients had central thrombocytopenia with diminished megakaryocytes (MK) and/or dysplasia, mean of RP 9.5% (CI 95%:5.6% 13.4%). Thirteen patients had high MK,mean of RP 25.7%(CI 95%:13.1% 38.3%). Six patients had normal MK, mean of RP 13.6% (CI 95%:0.6% 26.8%). There were differences between the group of increased MK and the group of central thrombocytopenias (p=0001). A value of RPe11% showed a sensitivity of 70% and specificity of 81% for the diagnosis of marrow aspirate with increased MK. Conclusions: RP are an indirect marker of megakaryocyte number in bone marrow. A value of RPe11% in patients with thrombocytopenia, especially with an acute onset, would indicate regenerative thrombocytopenia, while in the presence of low levels of RP a marrow aspiration should be performed (AU)