Detection and Molecular Characterization of GI-1 and GI-23 Avian Infectious Bronchitis Virus in Broilers Indicate the Emergence of New Genotypes in Bolivia.

Infectious Bronchitis Virus (IBV) is a major threat to the poultry industry worldwide, causing significant economic losses. While the virus's genetic structure is well understood, the specific strains circulating in Bolivia have remained uncharacterized until now. This study aimed to identify and characterize new IBV strains in Bolivia. Tissue samples from broilers exhibiting clinical signs of Infectious Bronchitis were screened to detect IBV using real-time RT-PCR (RT-qPCR). Positive samples with low cycle threshold (Ct) values were selected for sequencing the full S1 gene. Of the 12 samples analyzed, 10 were determined to be positive for IBV. However, only four samples yielded sufficient genetic material for sequencing and subsequent phylogenetic analysis. The results revealed the presence of GI-1 and GI-23 lineages, both belonging to genotype I (GI). The GI-1 lineage showed >99% sequence identity to the H120 and Massachusetts vaccine strains, suggesting a close relationship. In contrast, the GI-23 lineage clustered with other IBV strains, showing a distinct subclade that is genetically distant from Brazilian strains. No evidence of recombination was found. Furthermore, amino acid substitution analysis identified specific mutations in the S1 subunit, particularly in the hypervariable regions 1, 2, and 3. These mutations could potentially alter the virus's antigenicity, leading to reduced vaccine efficacy. The findings of this study highlight the importance of continued and broad genomic surveillance of circulating IBV strains and the need to improve vaccination strategies in Bolivia.

Salvage Endovascular Thrombectomy for Splenic Vein Thrombosis After Pancreas Transplantation: A Single-Center Experience and Systematic Literature Review.

OBJECTIVES: Technical graft loss, usually thrombotic in nature, accounts for most of the pancreas grafts that are removed early after transplant. Although arterial and venous thrombosis can occur, the vein is predominantly affected, with estimated overall rate of thrombosis of 6% to 33%. In late diagnosis, the graft will need to be removed because thrombectomy will not restore its functionality. However, in early diagnosis, a salvage procedure should be attempted. MATERIALS AND METHODS: We conducted a retrospective, descriptive analysis of a prospective database of patients who underwent pancreas transplant from April 2008 to June 2020 at a single center. We evaluated post-transplant clinical glucose levels, imaging, treatment, and outcomes. We also performed a systematic review of publications for endovascular treatment of vascular graft thrombosis in pancreas transplant. RESULTS: In 67 pancreas transplants analyzed, 13 (19%) were diagnosed with venous thrombus. In 7 of 13 patients (54%), systemic anticoagulation was prescribed because of a non-occlusive thromboses, resulting in complete resolution for all 7 patients. Six patients (46%) required endovascular thrombectomy because of the presence of complete occlusive thrombosis; 4 of these patients (67%) needed a second procedure because of recurrence of the thrombosis. One of the 6 patients (17%) required a surgical approach, resulting in successful removal of the recurrent clot. Twelve of the 13 grafts (92%) were rescued. Graft survival at 1 year was 84%; graft survival at 3, 5, and 10 years remained at 70%. CONCLUSIONS: Pancreas vein thrombosis represents a frequent surgical complication and remains as a challenging problem. In our experience, early diagnoses and an endovascular approach combined with aggressive medical treatment and follow-up can be used for successful treatment and reduce graft loss.

Efficacy and Safety of Aripiprazole in Borderline Personality Disorder: A Systematic Review.

Aripiprazole is an atypical antipsychotic medication, and its use in treating borderline personality disorder (BPD) is debatable because it is not FDA-approved for treating BPD. This study aimed to investigate the efficacy and safety of aripiprazole in patients with BPD. On July 2, 2021, the protocol (CRD42021256647) was registered in PROSPERO. PubMed, Scopus, Web of Science, Ovid-Medline, Embase, PsycINFO, and Cochrane (CENTRAL) were searched without regard for language or publication date. We also searched trial registries on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomized clinical trials with adult patients diagnosed with BPD met the inclusion criteria. The Cochrane risk of bias for randomized trials (RoB-2) method was used to assess the quality of the included studies. We included two previously published randomized clinical trials. There were 76 patients with BPD, with 38, 12, and 26 assigned to the aripiprazole, olanzapine, and placebo groups, respectively. Most patients (88.16%) were females, with ages ranging from 22.1 to 28.14 yr. Aripiprazole has been proven to reduce anxiety, depression, anger, hostility, clinical severity, and obsessive-compulsive behavior, insecurity, melancholy, anxiety, aggressiveness/hostility, phobic anxiety, paranoid thinking, psychoticism, and somatization. The adverse effects were headache, insomnia, restlessness, tremor, and akathisia. The risk of bias was considerable in both trials, which is somewhat problematic considering that prejudice can lead to incorrect outcomes and conclusions. Aripiprazole has demonstrated encouraging outcomes in the treatment of patients with BPD. More randomized controlled studies are needed.

Resección hepática laparoscópica versus hepatectomía abierta para lesiones benignas: estudio comparativo con propensity score matching / Laparoscopic liver resection versus open liver resection for benign lesions: a comparative study with propensity score matching

RESUMEN Antecedentes : las ventajas de la hepatectomía videolaparoscópica (HVL) hicieron que gane cada vez más campo para el tratamiento de los tumores hepáticos benignos (THB). Objetivo : comparar los resultados perioperatorios de pacientes sometidos a HVL con los de los operados con hepatectomía abierta (HA) por THB, emparejados con propensity score matching (PSM). Material y métodos : estudio descriptivo, retrospectivo y comparativo de HA y HVL por THB entre agosto de 2010 y junio de 2021. Se analizaron variables demográficas, preoperatorias, intraoperatorias y posoperatorias. Para evitar sesgos de las distintas covariables entre los grupos se realizó un PSM 1:1. Resultados : de 403 hepatectomías, se analizaron 82 por THB. De ellas 36 (44%) fueron HA y 46 (56%) HVL. Edad media 45 ±14 años, 65% mujeres. Tras realizar el PSM, quedaron dos grupos de 28 pacientes cada uno. En HA, 5 (18%) pacientes requirieron transfusiones y ninguno en HVL (p = 0,01). Las complicaciones mayores se presentaron en 4 (14%) pacientes en HA, y ninguna en HVL (p = 0,03). Se reoperaron 4 (14%) pacientes con HA y ningún paciente con HVL (p = 0,03). La estadía hospitalaria total fue significativamente mayor en las HA (p = 0,04). No se registraron muertes a los 90 días en ninguno de los dos grupos. Conclusión : la HVL por THB es una técnica segura y eficaz, ya que los pacientes presentaron menor requerimiento transfusional, número de reoperaciones, de complicaciones mayores y de estadía hospitalaria que con HA. Por las ventajas encontradas, la HVL podría ser considerada la técnica de elección en cirugía por THB.

ABSTRACT Background : The advantages of laparoscopic liver resection (LLR) have increased its use for the treatment of benign liver tumors (BLTs). Objective : The aim of this study was to compare the perioperative outcomes of patients undergoing LLR with those operated on with open liver resection (OLR) for BLTs using propensity score matching (PSM). Material and methods : We conducted a descriptive and retrospective study comparing OLRs with LLRs performed between August 2010 and June 2021. The demographic, perioperative, intraoperative and postoperative variables were analyzed. We used PSM with 1:1 matching to avoid biases of the different covariates between the groups. Results : Of 303 liver resections, 82 corresponded to BLTs and were included in the analysis; 36 (44%) were OLRs and 46 (56%) were LLRs. Mean age was 45 ±14 years and 65% were women. After PSM, two groups of 28 patients each were constituted. Five patients (18%) in the OLR group and none in the LLR required transfusions (p = 0.01). Major complications, occurred in 4 (14%) patients in the OLR group and in no cases in the LLR group (p = 0.03). Four (14%) undergoing OLR required reoperation versus no patients with LLR (p = 0.03). Total length of hospital stay was significantly longer in OLR (p = 0.04). There were no deaths in any of the groups within 90 days. Conclusion : LLR for BLTs is a safe and effective technique, with lower requirement for transfusions, fewer reoperations and major complications and shorter length of hospital stay than OLR, Therefore, LLR could be considered the surgical technique of choice for BLTs.

COVID-19 in immunocompromised children: comparison of SARS-CoV-2 viral load dynamics between the first and third waves.

SARS-CoV-2 dynamics across different COVID-19 waves has been unclear in immunocompromised children. We aimed to compare the dynamics of SARS-CoV-2 RNA viral load (VL) during the first and third waves of COVID-19 in immunocompromised children. A retrospective and longitudinal cohort study was conducted in a pediatric referral hospital of Argentina. The study included 28 admitted immunocompromised children with laboratory confirmed SARS-CoV-2 infection. Thirteen acquired the infection during COVID-19 first wave (May to August 2020, group 1 (G1)) and fifteen in the third wave (January to March 2022, group 2 (G2)). RNA viral load measure and its dynamic reconstruction were performed in nasopharyngeal swabs by validated quantitative, real time RT-PCR, and linear mixed-effects model, respectively. Of the 28 children included, 54% were girls, most of them had hemato-oncological pathology (57%), and the median age was 8 years (interquartile range (IQR): 3-13). The dynamic of VL was similar in both groups (P = 0.148), starting from a level of 5.34 log10 copies/mL (95% confidence interval (CI): 4.47-6.21) in G1 and 5.79 log10 copies/mL (95% CI: 4.93-6.65) in G2. Then, VL decayed with a rate of 0.059 (95% CI: 0.038-0.080) and 0.088 (95% CI: 0.058-0.118) log10 copies/mL per day since diagnosis and fell below the limit of quantification at days 51 and 39 after diagnosis in G1 and G2, respectively. Our results evidenced a longer viral RNA persistence in immunocompromised pediatric patients and no difference in VL dynamic between COVID-19 first wave-attributed to ancestral infections-and third wave-attributed to Omicron infections.

Expanding the genetic spectrum of TUBB1-related thrombocytopenia.

ß1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 ß1-tubulin variants, p.Cys12LeufsTer12, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu, and p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size, and a minority had no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp, and p.Gly109Glu variants deranged ß1-tubulin incorporation into the microtubular marginal ring in platelets but had a negligible effect on platelet activation, secretion, or spreading, suggesting that ß1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered ß1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.

Neoplasia papilomucinosa intraductal de páncreas: experiencia a 10 años, en un único centro / Intraductal papillary mucinous neoplasm of the pancreas: A 10-year experience at a single center

RESUMEN Antecedentes: Debido a la mejoría de los métodos diagnósticos, la incidencia de la neoplasia papilar mucinosa intraductal del páncreas (NPMI) ha aumentado en los últimos años. Objetivo: Presentar la experiencia en el manejo alejado de pacientes con NPMI en un centro de referencia. Material y métodos : Se realizó análisis retrospectivo de pacientes que consultaron al Servicio de Ci rugía General y HPB del Hospital Universitario Fundación Favaloro, por patología pancreática tumo ral entre enero de 2010 y diciembre de 2019. Los pacientes se clasificaron en 2 grupos: A) aquellos con diagnóstico en consultorio de NPMI y B) aquellos en los que la NPMI fue un hallazgo en la pieza quirúrgica (B). Resultados: Ochenta y seis pacientes fueron analizados: 79 (90%) se incluyeron en el grupo A y 7 en el grupo B. De los pacientes del grupo A, en 57 casos (66%) se decidió conducta expectante y seguimiento (AS). De los 22 pacientes restantes, 18 fueron operados (29%) (AC) y 4 tienen la cirugía pendiente. Para el grupo A, la supervivencia a los 5 años fue de 89% para el grupo AS, de 86% en grupo AC, y del 43% para el grupo B (Breslow 0,001, Log-Rank 0,001 vs. grupo A). Conclusión: El diagnóstico y manejo de la NPMI está hoy estandarizado, en las tipo I y III está indicada cirugía, la tipo II debe seguirse por riesgo de malignización; cuando se le indica cirugía, la supervivencia a largo plazo debe ser similar a la del grupo en seguimiento.

ABSTRACT Background: The incidence of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the past years along with the development of diagnostic imaging tests. Objective: The aim of this study is to describe our experience on long-term management of patients with IPMNs in a reference center. Material and methods: We conducted a retrospective and descriptive analysis of patients with pancreatic neoplasms followed-up at the Department of General Surgery and Hepato-Biliary Surgery, Hospital Universitario Fundación Favaloro, between January 2010 and December 2019. The patients were classified into 2 groups: group A (diagnosis of IPMN made in the outpatient clinic), and group B (diagnosis of IPMN in the pathological examination). Results: Eighty-six patients were analyzed: 79 (90%) in group A and 7 in group B. In group A, a watchful waiting with monitoring (AM) was decided in 57 cases (66%). Of the remaining 22 patients, 18 (29%) patients underwent surgery (AS) and 4 are waiting for surgery. Survival at 5 years was 89% in group AM, 86% in group AS and 43% in group B (Breslow 0.001, log-rank test 0,001 vs. group A). Conclusion : The diagnosis and management of IPMNs is currently standardized. Surgery is indicated in MD-IPMN and mixed type IPMN. Patients with BD-IPMN type should be monitored due to the risk of malignant transformation. When surgery is indicated, long-term survival should be similar to that of the surveillance group.

Rabdomiosarcoma paratesticular: Reporte de caso y revisión de la literatura / Paratesticular rhabdomyosarcoma: Case report and literature review

Objetivo:Ofrecer un alcance de la relevancia del diagnóstico oportuno del cáncer testicular, a partir de un caso infrecuente de rabdomiosarcoma paratesticular en un adulto. Se trata de un paciente varón Reporte de Caso:de 39 años, que ingresa al servicio de cirugía - urología por un aumento de volumen de contenido escrotal, de forma progresiva desde hace 2 años, con crecimiento paulatino de la masa. En la ecografía testicular se evidencia un notorio aumento de volumen de bolsas escrotales por aparente tumoración o masa de consistencia dura, de estructura heterogénea y aspecto sólido de bordes mal definidos. Considerando los hallazgos clínicos, marcadores testiculareseimagenológicossediagnosticóuntumorparatesticular derecho. Se realizó una orquiectomía derecha más exéresis de tumor paratesticular derecho. Patología concluyó en rabdomiosarcoma embrionario paratesticular con cápsula rota. Paciente fue dado de alta con seguimiento por consulta externa y referido a hospital oncológico de cuarto nivel.

Objetive:Offer a scope of the relevance of the timely diagnosis of testicular cancer, based on a infrequent case of paratesticular rhabdomyosarcoma in an adult.The patient is a 39-year-old male who was admitted to Case report:the urology-surgery department because of an increase in scrotal volume, which has been progressive over the past two years, with gradual growth of the mass. Testicular ultrasound shows a notorious increase in volume of scrotal bags due to an apparent tumour or mass of hard consistency, of heterogeneous structure and solid aspect with ill-defined edges. Considering the clinical findings, testicular markers and imaging, a right paratesticular tumor was diagnosed. Aright orchiectomy plus right paratesticular tumor exeresis was performed. Pathology concluded in paratesticular embryonic rhabdomyosarcoma with a broken capsule. Patient was discharged with outpatient follow-up and referred to the fourth level cancer hospital

Rabdomiosarcoma paratesticular: Reporte de caso y revisión de la literatura / Paratesticular rhabdomyosarcoma: Case report and literature review

RESUMEN Objetivo: Ofrecer un alcance de la relevancia del diagnóstico oportuno del cáncer testicular, a partir de un caso infrecuente de rabdomiosarcoma paratesticular en un adulto. Reporte de Caso: Se trata de un paciente varón de 39 años, que ingresa al servicio de cirugía - urología por un aumento de volumen de contenido escrotal, de forma progresiva desde hace 2 años, con crecimiento paulatino de la masa. En la ecografía testicular se evidencia un notorio aumento de volumen de bolsas escrotales por aparente tumoración o masa de consistencia dura, de estructura heterogénea y aspecto sólido de bordes mal definidos. Considerando los hallazgos clínicos, marcadores testiculares e imagenológicos se diagnosticó un tumor paratesticular derecho. Se realizó una orquiectomía derecha más exéresis de tumor paratesticular derecho. Patología concluyó en rabdomiosarcoma embrionario paratesticular con cápsula rota. Paciente fue dado de alta con seguimiento por consulta externa y referido a hospital oncológico de cuarto nivel.

ABSTRACT Objetive: Offer a scope of the relevance of the timely diagnosis of testicular cancer, based on a infrequent case of paratesticular rhabdomyosarcoma in an adult. Case report: The patient is a 39-year-old male who was admitted to the urology-surgery department because of an increase in scrotal volume, which has been progressive over the past two years, with gradual growth of the mass. Testicular ultrasound shows a notorious increase in volume of scrotal bags due to an apparent tumour or mass of hard consistency, of heterogeneous structure and solid aspect with ill-defined edges. Considering the clinical findings, testicular markers and imaging, a right paratesticular tumor was diagnosed. A right orchiectomy plus right paratesticular tumor exeresis was performed. Pathology concluded in paratesticular embryonic rhabdomyosarcoma with a broken capsule. Patient was discharged with outpatient follow-up and referred to the fourth level cancer hospital.

A decade of changes in management of immune thrombocytopenia, with special focus on elderly patients.

BACKGROUND: Ten years after their availability, thrombopoietin receptor agonists (TPO-RA) have heralded a paradigm shift in the treatment of immune thrombocytopenia (ITP). This study was aimed to analyze the implementation of current recommendations in the standard practice of adult ITP patients, and how age may influence those changes. METHODS: We included 121 adult patients (> 65 years, n = 54; younger individuals, n = 67) who initiated treatment with TPO-RA between January 2012 and December 2014. RESULTS: Patients older than 65 years treated with TPO-RA presented at diagnosis with significantly higher platelet counts, less bleeding, and a more prothrombotic profile than younger ones. The high efficacy rates of TPO-RA, preferentially used during the last decade in non-chronic phases, precluded from further therapies in the majority of ITP patients. Their administration was associated with a sharp decline in the last decade in the use of splenectomy and intravenous immunoglobulin, especially in younger ITP individuals. CONCLUSION: These results confirm (1) that there is a preferential use of TPO-RAs in elderly ITP patients with fewer bleeding complications but more unfavorable prothrombotic conditions than in younger individuals, and (2) that early use of these agents has been established as an effective therapeutic alternative to other second line therapies.

Progresión de casos de Coronavirus en Latinoamérica: Análisis comparativo a una semana de iniciada la pandemia en cada país / Progression of Coronavirus cases in Latin America: Comparative analysis one week after the start of the pandemic in each country

La pandemia generada por la COVID-19 progresa diferente cuando llega a cada territorio, se comparó la progresión de casos de Coronavirus en la primera semana de la pandemia en cada país en Latinoamérica. Se realizó un estudio descriptivo, con la información de los casos confirmados en cada país, esto desde que se anunciara el primer caso en cada territorio. Se muestran las progresiones en formas de gráficas, con los casos totales y ajustados por la densidad poblacional. Uruguay y Panamá fueron los países que destacaron de todos los evaluados, tuvieron una mayor cantidad de casos confirmados ponderados en la primera semana de la pandemia. Así mismo, estos dos países también fueron los que tuvieron mayor cantidad de casos absolutos (no ponderados por la cantidad de población), así como, el país de Venezuela; que incluso se piensa que tiene más casos, por sus problemas políticos. Hubo algunas diferencias en la cantidad de casos que se presentaron en cada país Latinoamericano al final de su primera semana de epidemia COVID-19; esto podría deberse a las políticas gubernamentales que se tomaron antes y durante esos primeros días, las cuales deben servir como ejemplo para el actuar en futuros casos similares

The pandemic generated by COVID-19 progresses differently when it reaches each territory, the progression of Coronavirus cases in the first week of the pandemic was compared in each country in Latin America. A descriptive study was carried out, with the information of the confirmed cases in each country, this since the first case was announced in each territory. Progressions are shown in graphical forms, with total cases and adjusted for population density. Uruguay and Panama were the countries that stood out from all those evaluated, they had a greater number of confirmed cases weighted in the first week of the pandemic. Likewise, these two countries were also those with the highest number of absolute cases (not weighted by the number of population), as well as the country of Venezuela; that he is even thought to have more cases, due to his political problems. There were some differences in the number of cases that occurred in each Latin American country at the end of its first week of the COVID-19 epidemic; this could be due to the government policies that were taken before and during those first days, which should serve as an example for acting in future similar cases

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia.

Very few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 109/l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs. eltrombopag (P = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs. 2.2%, P < 0.001), and to previous splenectomy in younger patients (100% vs. 33%, P = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA.

High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study.

Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.

Identification of 58 Mutations (26 Novel) in 94 of 109 Symptomatic Spanish Probands with Protein C Deficiency.

Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is available. We analyzed the PC gene (PROC) in 109 patients with symptomatic PC deficiency and in 342 relatives by sequencing the 9 PROC exons and their flanking intron regions. In 93 probands, we found 58 different mutations (26 novel). Thirty-seven consisted of a nucleotide change, mainly missense mutations, 1 was a 6-nucleotide insertion causing the duplication of 2 amino acids, and 4 were deletions of 1, 3, 4, and 16 nucleotides. Nine mutations caused type II deficiencies, with the presence of normal antigen levels but reduced anticoagulant activity. Using a PC level of 70% as lowest normal limit, we found no mutations in 16 probands and 25 relatives with PC levels ≤ 70%. On the contrary, 4 probands and 12 relatives with PC levels > 70% carried the mutation identified in the proband. The spectrum of recurrent mutations in Spain is different from that found in the Netherlands, where the most frequent mutations were p.Gln174* and p.Arg272Cys, and is more similar to that found in France, where the most frequent were p.Arg220Gln and p.Pro210Leu. In our study, p.Val339Met (9 families), p.Tyr166Cys (7), p.Arg220Gln (6), and p.Glu58Lys (5) were the most prevalent. This study confirms the considerable heterogeneity of the genetic abnormality in PC deficiencies, and allowed genetic counseling to those individuals whose PC levels were close to the lower limit of the normal reference range.

Involvement of antifactor VIII autoantibodies specificity in the outcome of inhibitor eradication therapies in acquired hemophilia a patients.

: We hypothesized that inhibitor specificity may predict the outcome of antifactor VIII autoantibodies eradication treatment in acquired hemophilia A. Our objective was to analyze the association between factor VIII domains recognized by inhibitors and outcome of the immunosuppressive therapies (ISTs) in a prospective, observational study. 16 patients were recruited. Inhibitor specificities were assessed at diagnosis and throughout the study. Their association with IST outcome was addressed. First-line IST succeeded in 56% of patients. Inhibitors reacted mainly with light chain domains (69%) and/or the A2 domain (44%). 31% inhibitors recognized more than one domain. Significantly, the number of patients whose inhibitors recognized the light chain was significantly higher in the group of those who did not reach complete remission after first line IST when compared with those who did [6/7 (85.7%) vs. 4/9 (44.4%), P < 0.05]. Therefore, inhibitor specificity could predict the success of IST in acquired hemophilia A.

Apendicectomías: ¿llega tarde el paciente o las complicamos nosotros? / Appendicectomies: Does the patients arrive late or otherwise are complicated by us?

Appendicitis is the inflammation of the vermiform appendix. Acute appendictis is the most common surgical emergency, and the most frequent cause of abdominal pain. It is considered that between 7 to 12% of the world population will develop the disease in some ciurcumstances of their lifes, being more frequent during the second and third decades. The aim of this study was to evaluate the comlications derivated from the delay in the anagement of the patients with this complaint. Usually, the signs and symptoms are frequently typical and the diagnosis quickly made. However, the classic syndrome may not be evident and the correct diagnosis may be obscure, in whom a delay in diagnosis can result in a lifebreatening situation. Inflammation of the appendix usually results from the obstruction of the appendiceal lumen. The diagnosis of appendicitis depends primarily on the history and physical findings, but confirmation of the diagnosis usually requires appropriate laboratory, radiographic or endoscopic studies. Pain is usually the first simptom. vomiting usually develops. Acute appendicitis should always be included in the differential diagnosis of abdominal pain. Low-grade fewer is usual. The most characteristic sign is point tenderness at Mc-Burney's pint, which is located one third of the distance from the anterior-superior iliac spine to the umbilicus.We present a retrospective analysis, descriptive and observational. In our study the Alvarado score was empliye. The complications observed are detailed, and the results obtained are commented

A propósito de un caso de lipoma retroperitoneal / Retroperitoneal Lipoma: A case report

Los lipomas retroperitoneales son infrecuentes y suelen representar el 2.9% de los tumores primarios de origen en retroperitoneo1 . Pueden alcanzar gran tamaño y el diagnóstico diferencial debe hacer con el liposarcoma bien diferenciado, aunque es muy difícil de realizar en el preoperatorio2 . Se presenta el caso de un paciente con lipoma retroperitoneal cuyo diagnóstico se realizó por tomografía axial computada (TAC) y que fue extirpado en su totalidad.

Retroperitoneal lipomas are infrequent and can represent a 2.9 % of the primary tumors originated in the retroperitoneum. They can reach a great size and the differential diagnosis must be performed with the well differentiated liposarcoma, even though it is very difficult to establish it during the preoperative time. We describe herein a case of a patient with a retroperitoneal lipoma. The diagnosis was established with a computed axial tomography (CAT) and it was totally surgically removed.

Introducing high-throughput sequencing into mainstream genetic diagnosis practice in inherited platelet disorders.

Inherited platelet disorders are a heterogeneous group of rare diseases, caused by inherited defects in platelet production and/or function. Their genetic diagnosis would benefit clinical care, prognosis and preventative treatments. Until recently, this diagnosis has usually been performed via Sanger sequencing of a limited number of candidate genes. High-throughput sequencing is revolutionizing the genetic diagnosis of diseases, including bleeding disorders. We have designed a novel high-throughput sequencing platform to investigate the unknown molecular pathology in a cohort of 82 patients with inherited platelet disorders. Thirty-four (41.5%) patients presented with a phenotype strongly indicative of a particular type of platelet disorder. The other patients had clinical bleeding indicative of platelet dysfunction, but with no identifiable features. The high-throughput sequencing test enabled a molecular diagnosis in 70% of these patients. This sensitivity increased to 90% among patients suspected of having a defined platelet disorder. We found 57 different candidate variants in 28 genes, of which 70% had not previously been described. Following consensus guidelines, we qualified 68.4% and 26.3% of the candidate variants as being pathogenic and likely pathogenic, respectively. In addition to establishing definitive diagnoses of well-known inherited platelet disorders, high-throughput sequencing also identified rarer disorders such as sitosterolemia, filamin and actinin deficiencies, and G protein-coupled receptor defects. This included disease-causing variants in DIAPH1 (n=2) and RASGRP2 (n=3). Our study reinforces the feasibility of introducing high-throughput sequencing technology into the mainstream laboratory for the genetic diagnostic practice in inherited platelet disorders.

Predictors of students' adjustment during transition to university in Spain.

BACKGROUND: Adjustment to university is a major life transition that not all emerging adults manage successfully. The Student University Adjustment Questionnaire is the instrument most commonly used to evaluate this multidimensional construct. Research in Spain on the predisposing factors for successful adjustment to university in emerging adults is scarce relative to the large number of studies carried out in North America. The objective of the present study was to analyze the association between students’ gender, family background, pre-university achievement and adjustment to university. METHOD: Participants were 300 Spanish first-year students (198 women and 102 men) of mean age 18.02 years. RESULTS: Pre-university achievement was the only significant predictor of academic, social and institutional adjustment. Gender directly affected personal-emotional adjustment and indirectly affected academic adjustment mediated by entry grade. CONCLUSIONS: Students’ entry characteristics predict adjustment to university in the first year. These findings have important theoretical and practical implications.