Middle-age abolishes cardioprotection conferred by thioredoxin-1 in mice.

Thioredoxin-1 (Trx1) has cardioprotective effects on ischemia/reperfusion (I/R) injury, although its role in ischemic postconditioning (PostC) in middle-aged mice is not understood. This study aimed to evaluate if combining two cardioprotective strategies, such as Trx1 overexpression and PostC, could exert a synergistic effect in reducing infarct size in middle-aged mice. Young or middle-aged wild-type mice (Wt), transgenic mice overexpressing Trx1, and dominant negative (DN-Trx1) mutant of Trx1 mice were used. Mice hearts were subjected to I/R or PostC protocol. Infarct size, hydrogen peroxide (H2O2) production, protein nitration, Trx1 activity, mitochondrial function, and Trx1, pAkt and pGSK3ß expression were measured. PostC could not reduce infarct size even in the presence of Trx1 overexpression in middle-aged mice. This finding was accompanied by a lack of Akt and GSK3ß phosphorylation, and Trx1 expression (in Wt group). Trx1 activity was diminished and H2O2 production and protein nitration were increased in middle-age. The respiratory control rate dropped after I/R in Wt-Young and PostC restored this value, but not in middle-aged groups. Our results showed that Trx1 plays a key role in the PostC protection mechanism in young but not middle-aged mice, even in the presence of Trx1 overexpression.

Transplant renal artery stenosis: Study of incidence using doppler ultrasound, risk factors and analysis is effect in graft outcomes.

INTRODUCTION AND OBJECTIVES: Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation which estimated incidence is 13%. It could cause refractory arterial hypertension, kidney dysfunction and premature death in transplant recipients. METHODS: We carried out a retrospective study including every patient who underwent renal transplantation between 2014 and 2020. They were evaluated with a systematic post-transplant renal Doppler ultrasound. To identify independent risk factors for transplant renal artery stenosis we performed a multivariate analysis. RESULTS: Seven hundred twenty-four kidney transplants were included, 12% ​​were living donors and 88% were deceased donors. The mean age was 54.8 in recipients and 53 in donors. Transplant renal artery stenosis was diagnosed in 70 (10%) recipients, the majority in the first 6 months after surgery. 51% of patients with transplant renal artery stenosis were managed conservatively. The multivariate analysis showed diabetes mellitus, graft rejection, arterial resuture and donor body mass index as independent risk factors for transplant renal artery stenosis. Survival of the grafts with transplant renal artery stenosis was 98% at 6 months and 95% at two years. CONCLUSIONS: The systematic performance of Doppler ultrasound in the immediate post-transplant period diagnosed 10% of transplant renal artery stenosis in our cohort. Despite the above risk factors, an adequate monitoring and treatment could avoid the increased risk of graft loss in patients with transplant renal artery stenosis.

Management of acute postoperative pain: Conditions to guarantee the safety and effectiveness of analgesic treatments.

The evidence on postoperative pain management is of low or insufficient quality. The SEDAR Acute Pain Working Group has prepared this guideline-document to apply the best available scientific evidence to clinical practice, individualizing it based on factors specific to the patient and the procedure, and encompassing different organizational options, attempting to individualize it based on specific factors of the patient and the procedure, and encompassing the different organizational options for pain control. The document updates concepts and minimum requirements necessary for optimal postoperative analgesia, a multidisciplinary approach and the management of Acute Postoperative Pain. Strategic lines and different management models are defined. A general perioperative action plan is established based on collaboration with the surgical departments involved, on the joint review of the evidence and on preparation of protocols by the procedure. Finally, a follow-up plan and a series of minimum indicators necessary for quality control of postoperative pain are presented.

Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation.

INTRODUCTION: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = -0.547; 95% CI, -0.610 to -0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

[Translated article] Metal on metal total hip arthroplasty: Correlation between inclination of the acetabular and metal ion levels.

Due to their low friction index, hip arthroplasties with metal-metal (M-M) friction torque have been an attractive option in young patients with high functional demand, currently they have suffered a decrease in their use due to the complications of some models and physiological reactions adverse reactions related to the elevation of metal ions in the blood. Our objective is to review the patients with M-M pair operated in our centre, correlating the ion level with the position of the acetabular component and with the size of the head. MATERIAL AND METHODS: Retrospective review of 166 M-M hip prostheses operated between 2002 and 2011. Sixty five ruled out for different causes (death, loss of follow-up, no current ion control, no radiography or others), leaving a sample of 101 patients to be analysed. Follow-up time, cup inclination angle, blood ion level, Harris Hip Score (HHS), and complications were recorded. RESULTS: One hundred and one patients (25 women and 76 men), 55 years of average age (between 26 and 70), of these 8 were surface prostheses and 93 total prostheses. The mean follow-up time was 10 years (between 5 and 17 years). The mean head diameter was 46.25 (between 38 and 56). The mean inclination of the butts was 45.7° (between 26° and 71°). The correlation force between the verticality of the cup and the increase in ions is moderate r=0.31 for Cr and slight r=0.25 for Co. The correlation force between head size and ion increase is weak and inverse r=-0.14 for Cr and r=0.1 for Co. Five patients (4.9%) required revision (2 [1%] due to increased ions with pseudotumor). The mean time to revision was 6.5 years in which the ions increased. The mean HHS was 94.01 (between 55.8 and 100). In the review of patients, we found 3 with a significant increase in ions who had not followed controls, all 3 had an HHS of 100. The angles of the acetabular components were 69°, 60° and 48° and the diameter of the head was 48.42 and 48mm, respectively. DISCUSSION AND CONCLUSIONS: M-M prostheses have been a valid option in patients with high functional demand. A bi-annual analytical follow-up is recommended, since in our case we have detected 3 patients with HHS 100 who presented unacceptable elevation of cobalt >20µm/l (according to SECCA) of the ions and 4 with very abnormal elevation of cobalt ≥10µm/l (according to SECCA), all of them with cup orientation angles >50°. With our review we can conclude that there is a moderate correlation between the verticality of the acetabular component and the increase in blood ions and that the follow-up of this patient with angles >50° is essential.

Association between arterial stiffness and fat mass in patients with obesity.

OBJECTIVE: The aim is to observe whether body composition in patients with high-risk obesity (body mass index >35 or between 30 and 34.9kg/m2 with a waist circumference greater than 102cm in men or greater than 88cm in women) is related with vascular disease. METHODS: This is a cross-sectional study of patients with high-risk obesity. Their fat mass was measured through bioimpedance and arterial stiffness through pulse wave velocity (PWV). Tertiles of patients were analyzed according to PWV distribution. RESULTS: A total of 59 patients were analyzed. As PWV increased, BMI (p=0.02) and fat mass content (p<0.00) increased. There was also a significant increase in inflammation indicators. CONCLUSIONS: In patients with high-risk obesity, there were differences in their body composition which were associated with changes in arterial stiffness and inflammatory burden.

Metal on metal total hip arthroplasty: Correlation between inclination of the acetabular and metal ion levels. / Artroplastias metal-metal en cadera: correlación entre el aumento de iones y el ángulo del componente acetabular.

Due to their low friction index, hip arthroplasties with metal-metal (M-M) friction torque have been an attractive option in young patients with high functional demand, currently they have suffered a decrease in their use due to the complications of some models and physiological reactions adverse reactions related to the elevation of metal ions in the blood. Our objective is to review the patients with M-M pair operated in our center, correlating the ion level with the position of the acetabular component and with the size of the head. MATERIAL AND METHODS: Retrospective review of 166 M-M hip prostheses operated between 2002 and 2011. Sixty five ruled out for different causes (death, loss of follow-up, no current ion control, no radiography or others), leaving a sample of 101 patients to be analyzed. Follow-up time, cup inclination angle, blood ion level, Harris Hip Score (HHS), and complications were recorded. RESULTS: One hundred and one patients (25 women and 76 men), 55years of average age (between 26 and 70), of these 8 were surface prostheses and 93 total prostheses. The mean follow-up time was 10years (between 5 and 17years). The mean head diameters was 46.25 (between 38 and 56). The mean inclination of the butts was 45.7° (between 26° and 71°). The correlation force between the verticality of the cup and the increase in ions is moderate r=0.31 for Cr and slight r=0.25 for Co. The correlation force between head size and ion increase is weak and inverse r=-0.14 for Cr and r=0.1 for Co. Five patients (4.9%) required revision (2 [1%] due to increased ions with pseudotumor). The mean time to revision was 6.5years in which the ions increased. The mean HHS was 94.01 (between 55.8 and 100). In the review of patients, we found 3 with a significant increase in ions who had not followed controls, all 3 had an HHS of 100. The angles of the acetabular components were 69°, 60° and 48° and the diameter of the head was 48.42 and 48mm, respectively. DISCUSSION AND CONCLUSIONS: M-M prostheses have been a valid option in patients with high functional demand. A bi-annual analytical follow-up is recommended, since in our case we have detected 3patients with HHS100 who presented unacceptable elevation of cobalt >20µm/L (according to SECCA) of the ions and 4 with very abnormal elevation of cobalt ≥10µm/L (according to SECCA), all of them with cup orientation angles >50°. With our review we can conclude that there is a moderate correlation between the verticality of the acetabular component and the increase in blood ions and that the follow-up of this patient with angles >50° is essential.

[Risks, phenotypes and comparison between treatments according to guidelines GOLD and GesEPOC in primary care]. / Riesgos, fenotipos y comparación de tratamiento de EPOC en atención primaria según guías GOLD y GesEPOC.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an underdiagnosed pathology with a high morbidity and mortality. Diagnosis and follow-up are mostly carried out in primary care (PC). The objective of our study is to classify COPD patients according to GOLD 2019 and GesEPOC 2017 guidelines. As secondary objectives, to analyze the type of risk and to describe and compare the prescribed treatment with that recommended by the guidelines. MATERIAL AND METHODS: Multicenter cross-sectional observational study in seven Health Care centers. 637 COPD patients between 35 and 85years old were included. RESULTS: The mean age was 70.3years old, 84.6% had comorbidities and 43.5% were active smokers. The mean post-bronchodilator FEV1 was 61.92% (SD: 17.42). Most are patients with mMRC=1 (43.8%), 57.8% CAT<10. Mild BODEx index (75.7%). GoldA was the majority (47.7%). The most frequent phenotype was non-exacerbator (61.1%). 25% were ACOs. 56.2% were low-risk patients. 20.6% had not been prescribed any treatment, LABA +LAMA +CI (19.6%), LAMA +LABA (16.5%) and LAMA (16.3%). If we compare the treatments that the patients have prescribed, with the one is recommended by GOLD, we obtain that 61% coincide with moderate concordance, while if we compare with GesEPOC, 53.8% coincide with weak concordance. 73.4% of the treatments coincide between both documents (moderate agreement). CONCLUSIONS: COPD patients treated in PC are low risk, mild and non-exacerbators. If we compare the treatments that the patients have prescribed, with what is recommended by GOLD and GesEPOC, we find a moderate and weak concordance, respectively.

New ultrasound-guided capsular blocks for hip surgery: A narrative review.

Surgery on the hip joint is very common. Improving pain management has been and is one of the fundamental pillars to optimize the functional recovery of patients. To do this, we must design a multimodal anesthetic-analgesic plan that covers the entire perioperative period. Peripheral nerve blocks and fascial blocks are an important component of multimodal analgesic strategies. Traditional blocks have moderate efficacy, prolonged motor impairment, and increased risk of falls. As an alternative, capsular blocks ("ileopsoas plane block" or "IPB" and pericapsular nerve group block or "PENG block") have recently been described that aim to avoid motor impairment while maintaining optimal analgesic efficacy. The objective of this review is to describe the new capsular blocks and to analyze whether they allow to improve postoperative analgesia and promote functional recovery with fewer complications, based on the innervation of the hip. To do this, a bibliographic review was carried out in the PubMed, Embase and Cochrane Library databases from January 2018 to June 2020.

Variant rs4149584 (R92Q) of the TNFRSF1A gene in patients with familial multiple sclerosis.

INTRODUCTION: Genomic studies have identified numerous genetic variants associated with susceptibility to multiple sclerosis (MS); however, each one explains only a small percentage of the risk of developing the disease. These variants are located in genes involved in specific pathways, which supports the hypothesis that the risk of developing MS may be linked to alterations in these pathways, rather than in specific genes. We analyzed the role of the TNFRSF1A gene, which encodes one of the TNF-α receptors involved in a signaling pathway previously linked to autoimmune disease. METHODS: We included 138 individuals from 23 families including at least 2 members with MS, and analyzed the presence of exonic variants of TNFRSF1A through whole-exome sequencing. We also conducted a functional study to analyze the pathogenic mechanism of variant rs4149584 (-g.6442643C > G, NM_001065.4:c.362 G > A, R92Q) by plasmid transfection into human oligodendroglioma (HOG) cells, which behave like oligodendrocyte lineage cells; protein labeling was used to locate the protein within cells. We also analyzed the ability of transfected HOG cells to proliferate and differentiate into oligodendrocytes. RESULTS: Variant rs4149584 was found in 2 patients with MS (3.85%), one patient with another autoimmune disease (7.6%), and in 5 unaffected individuals (7.46%). The 2 patients with MS and variant rs4149584 were homozygous carriers and belonged to the same family, whereas the remaining individuals presented the variant in heterozygosis. The study of HOG cells transfected with the mutation showed that the protein does not reach the cell membrane, but rather accumulates in the cytoplasm, particularly in the endoplasmic reticulum and near the nucleus; this suggests that, in the cells presenting the mutation, TNFRSF1 does not act as a transmembrane protein, which may alter its signaling pathway. The study of cell proliferation and differentiation found that transfected cells continue to be able to differentiate into oligodendrocytes and are probably still capable of producing myelin, although they present a lower rate of proliferation than wild-type cells. CONCLUSIONS: Variant rs4149584 is associated with risk of developing MS. We analyzed its functional role in oligodendrocyte lineage cells and found an association with MS in homozygous carriers. However, the associated molecular alterations do not influence the differentiation into oligodendrocytes; we were therefore unable to confirm whether this variant alone is pathogenic in MS, at least in heterozygosis.

CYB5R3 homozygous pathogenic variant as a rare cause of cyanosis in the newborn.

Detailed below is a very illustrative case of a rare pathology of recessive congenital methemoglobinemia. The patient, a newborn female, was homozygous for c.535G > A, p.(Ala179Thr) a pathogenic variant in the CYB5R3 gene. The reported population frequency of the allele is 0.853%, demonstrating why it is remarkable to find both parents are heterozygous carriers without consanguinity. A brief review of previously published cases is also presented.

Centenary of epidural anaesthesia.

March 2021 marked the first centenary of the publication of Fidel Pagés Miravé's seminal article Anestesia metamérica in the Revista Española de Cirugía. Pagés' knowledge of Bier and Tuffier's intradural (1889-1900) and Gil Vernet's sacral (1917-1918) techniques played a pivotal role in the development of the epidural anesthesia technique. Fidel Pagés' extensive experience with treating the casualties of armed conflicts, his proficiency in French and German, and his vast knowledge of anatomy, physiology and pharmacology lie behind the accuracy with which he describes the different approaches, the different anesthetic solutions, or the different instruments used, and the indications, contraindications and complications associated with his technique. In the centenary of his article, we would like to thank Fidel Pagés' for describing an anesthetic and analgesic technique that has improved the lives of so many patients.

Colorenal fistula and urinary tract infection in a pediatric patient with acute lymphoblastic leukemia. / Fístula colorrenal e infección de vías urinarias en paciente pediátrico con leucemia linfoide aguda.

INTRODUCTION: Colorenal fistula is rare in the pediatric population. It may occur at any segment involved by ischemia, chronic inflammation, or necrosis. It is typically associated with a preliminary renal lesion that may arise as a result of interventional procedures, inflammatory conditions, colon tumor, and xanthogranulomatous pyelonephritis, among others. CASE REPORT: 15-year-old female patient diagnosed with acute lymphoblastic leukemia admitted at our institution for baseline condition management. During her stay, she experienced gastrointestinal and urinary infectious events. In the assessment and management of those, a left colorenal fistula was found. Surgical treatment was decided upon. DISCUSSION: Colorenal fistula typically occurs secondary to renal inflammation or infection. Clinical signs are highly variable, and treatment is surgical, with the fistulous tract being resected in all cases.

INTRODUCCION: Las fístulas colorrenales son infrecuentes en la población pediátrica. Pueden desarrollarse en cualquier segmento afectado por isquemia, inflamación crónica o necrosis. Suelen estar asociadas a una lesión primitiva en el riñón que puede producirse por procedimientos intervencionistas, enfermedades inflamatorias, tumorales del colon, pielonefritis xantogranulomatosa, entre otras. CASO CLINICO: Paciente femenina de 15 años, con diagnóstico de leucemia linfoide aguda, ingresa a la institución para recibir manejo de su enfermedad de base. Durante su evolución, desarrolla eventos infecciosos (gastrointestinales y urinarios), y en evaluación y manejo de estos se documenta fístula colorrenal izquierda, motivo por el cual se da un enfoque de tratamiento quirúrgico. COMENTARIOS: La fístula renocólica generalmente se presenta secundaria a procesos inflamatorios o infecciosos renales; su presentación clínica es muy variada, y el tratamiento es quirúrgico, incluyendo siempre la resección del trayecto fistuloso.