SARS-CoV-2 variant spike and accessory gene mutations alter pathogenesis.

The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the spike protein. Although these differences in spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome that may also affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through interference with innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other nonspike mutations on SARS-CoV-2 pathogenesis, we synthesized both viruses possessing deletions in the accessory genes as well as viruses where the WA-1 spike is replaced by each variant spike gene in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to both WA-1 and the full variant viruses. Our work has revealed that the accessory proteins contribute to SARS-CoV-2 pathogenesis and the nonspike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host. This work suggests that while spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may alter clinical disease presentation.

Atomistic simulations of calcium aluminosilicate interfaced with liquid water.

The dissolution behavior of calcium aluminosilicate based glass fibers, such as stone wool fibers, is an important consideration in mineral wool applications for both the longevity of the mineral wool products in humid environments and limiting the health impacts of released and inhaled fibers from the mineral wool product. Balancing these factors requires a molecular-level understanding of calcium aluminosilicate glass dissolution mechanisms, details that are challenging to resolve with experiment alone. Molecular dynamics simulations are a powerful tool capable of providing complementary atomistic insights regarding dissolution; however, they require force fields capable of describing not-only the calcium aluminosilicate surface structure but also the interactions relevant to dissolution phenomena. Here, a new force field capable of describing amorphous calcium aluminosilicate surfaces interfaced with liquid water is developed by fitting parameters to experimental and first principles simulation data of the relevant oxide-water interfaces, including ab initio molecular dynamics simulations performed for this work for the wüstite and periclase interfaces. Simulations of a calcium aluminosilicate surface interfaced with liquid water were used to test this new force field, suggesting moderate ingress of water into the porous glass interface. This design of the force field opens a new avenue for the further study of calcium and network-modifier dissolution phenomena in calcium aluminosilicate glasses and stone wool fibers at liquid water interfaces.

[Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters]. / Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa.

Background: COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; < 5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion: When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease.

M1 and M2 mAChRs activate PDK1 and regulate PKC ßI and ε and the exocytotic apparatus at the NMJ.

Neuromuscular junctions (NMJ) regulate cholinergic exocytosis through the M1 and M2 muscarinic acetylcholine autoreceptors (mAChR), involving the crosstalk between receptors and downstream pathways. Protein kinase C (PKC) regulates neurotransmission but how it associates with the mAChRs remains unknown. Here, we investigate whether mAChRs recruit the classical PKCßI and the novel PKCε isoforms and modulate their priming by PDK1, translocation and activity on neurosecretion targets. We show that each M1 and M2 mAChR activates the master kinase PDK1 and promotes a particular priming of the presynaptic PKCßI and ε isoforms. M1 recruits both primed-PKCs to the membrane and promotes Munc18-1, SNAP-25, and MARCKS phosphorylation. In contrast, M2 downregulates PKCε through a PKA-dependent pathway, which inhibits Munc18-1 synthesis and PKC phosphorylation. In summary, our results discover a co-dependent balance between muscarinic autoreceptors which orchestrates the presynaptic PKC and their action on ACh release SNARE-SM mechanism. Altogether, this molecular signaling explains previous functional studies at the NMJ and guide toward potential therapeutic targets.

Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?

The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is poor in those receiving immunosuppressive therapy and glucocorticoids in particular. Despite the effectiveness of cotrimoxazole against PJP, the risk of adverse effects remains significant, and no consensus has emerged regarding the need for PJP prophylaxis in SARD patients undergoing immunosuppressor therapies.Objective: To evaluate the efficacy and safety of cotrimoxazole prophylaxis against PJP in SARD adult patients receiving immunosuppressive therapies. Methods: We performed a systematic review, consulting MEDLINE, EMBASE, and Cochrane Library databases up to April 2020. Outcomes covered prevention of PJP, other infections, morbidity, mortality, and safety. The information obtained was summarized with a narrative review and results were tabulated. Of the 318 identified references, 8 were included. Two were randomized controlled trials and six observational studies. The quality of studies was moderate or low. Despite disparities in the cotrimoxazole prophylaxis regimens described, results were consistent in terms of efficacy, particularly with glucocorticoid doses > 20 mg/day. However, cotrimoxazole 400 mg/80 mg/day, prescribed three times/ week, or 200 mg/40 mg/day or in dose escalation, exhibited similar positive performances. Conversely, cotrimoxazole 400 mg/80 mg/day showed higher incidences of withdrawals and adverse effects. Cotrimoxazole prophylaxis against PJP exhibited efficacy in SARD, mainly in patients taking glucocorticoids ≥ 20 mg/day. All cotrimoxazole regimens exposed seemed equally efficacious, although, higher quality trials are needed. Adverse effects were observed 2 months after initiation, particularly with the 400 mg/80 mg/day regimen. Conversely, escalation dosing or 200 mg/40 mg/day regimens appeared better tolerated.

From transformation to chronification of migraine: pathophysiological and clinical aspects.

Chronic migraine is a neurological disorder characterized by 15 or more headache days per month of which at least 8 days show typical migraine features. The process that describes the development from episodic migraine into chronic migraine is commonly referred to as migraine transformation or chronification. Ample studies have attempted to identify factors associated with migraine transformation from different perspectives. Understanding CM as a pathological brain state with trigeminovascular participation where biological changes occur, we have completed a comprehensive review on the clinical, epidemiological, genetic, molecular, structural, functional, physiological and preclinical evidence available.

[Neurological complications in critical patients with COVID-19]. / Complicaciones neurológicas en pacientes críticos por SARS-CoV-2.

Introduction: We analysed the neurological complications of patients with severe SARS-CoV-2 infection who required intensive care unit (ICU) admission. Patients and methods: We conducted a retrospective, observational, descriptive study of consecutive patients admitted to the ICU due to severe respiratory symptoms secondary to SARS-CoV-2 infection between 1 April and 1 June 2020. Results: We included 30 patients with neurological symptoms; 21 were men (72.40%), and mean age (standard deviation [SD]) was 57.41 years (11.61). The mean duration of ICU stay was 18.83 days (14.33). The neurological conditions recorded were acute confusional syndrome in 28 patients (93.33%), neuromuscular disease in 15 (50%), headache in 5 (16.66%), cerebrovascular disease in 4 (13.33%), and encephalopathies/encephalitis in 4 (13.33%). CSF analysis results were normal in 6 patients (20%). Brain MRI or head CT showed alterations in 20 patients (66.6%). EEG was performed in all patients (100%), with 8 (26.66%) showing abnormal findings. In 5 of the 15 patients with clinical myopathy, diagnosis was confirmed with electroneuromyography. We found a correlation between older age and duration of ICU stay (P = .002; 95% CI: 4.032-6.022; OR: 3,594). Conclusions: Severe COVID-19 mainly affects men, as observed in other series. Half of our patients presented acute myopathy, and almost all patients left the ICU with acute confusional syndrome, which fully resolved; no correlation was found with EEG or neuroimaging findings. Older age is associated with longer ICU stay.

Comorbidity and prognostic factors on admission in a COVID-19 cohort of a general hospital. / Comorbilidad y factores pronósticos al ingreso en una cohorte COVID-19 de un hospital general.

ANTECEDENTS AND OBJECTIVE: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. MATERIAL AND METHODS: Retrospective cohort study of patients with COVID-19 admitted from 26th February, who had been discharged or died, up to 29th April, 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. RESULTS: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV-2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) and cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335UI/L, and 193 vs 121mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH≥345IU/L (CI 95% OR 1,52-46,00), and age≥65 years (CI 95% OR 1,23-44,62). CONCLUSIONS: The presence of cardiopathy, levels of LDH≥345IU/L and age ≥65 years are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.

The effect of age and sex on the diagnostic yield of the echocardiogram in patients with syncope. / Efecto de la edad y el sexo en el rendimiento diagnóstico del ecocardiograma en pacientes con síncope.

INTRODUCTION: Syncope is the motivation for numerous diagnostic tests, among them transthoracic echocardiography (TTE); however, previous evidence suggests there is little utility in this test. Our objective was to assess its diagnostic yield in syncope, analysing the effect of age and sex. MATERIAL AND METHODS: We conducted an observational study that included patients with syncope and who underwent TTE between 1990-2015. We defined diagnostic findings related to syncope and performed a descriptive analysis, assessing the diagnostic yield (overall and according to age and sex). RESULTS: The study included 3,302 patients and measured a diagnostic yield of 8.8%; the most common finding was ventricular dysfunction (4.5%). The probability of a diagnostic TTE significantly increased with age (p<.001) but was low for patients younger than 50 years (2.3%). The male sex was significantly related with a diagnostic TTE (p<.001), mostly due to the higher rate of ventricular dysfunction. CONCLUSIONS: The diagnostic yield of TTE in patients with syncope is moderate, low in patients younger than 50 years and lower in women than in men. These factors should be considered when conducting a diagnostic study of patients with syncope.

Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity.

Spinocerebellar ataxia type 7 is a neurodegenerative inherited disease caused by a CAG expansion in the coding region of the ATXN7 gene, which results in the synthesis of polyglutamine-containing ataxin-7. Expression of mutant ataxin-7 disturbs different cell processes, including transcriptional regulation, protein conformation and clearance, autophagy, and glutamate transport; however, mechanisms underlying neurodegeneration in SCA7 are still unknown. Implication of oxidative stress in the pathogenesis of various neurodegenerative diseases, including polyglutamine disorders, has recently emerged. We perform a cross-sectional study to determine for the first time pheripheral levels of different oxidative stress markers in 29 SCA7 patients and 28 age- and sex-matched healthy subjects. Patients with SCA7 exhibit oxidative damage to lipids (high levels of lipid hydroperoxides and malondialdehyde) and proteins (elevated levels of advanced oxidation protein products and protein carbonyls). Furthermore, SCA7 patients showed enhanced activity of various anti-oxidant enzymes (glutathione reductase, glutathione peroxidase, and paraoxonase) as well as increased total anti-oxidant capacity, which suggest that activation of the antioxidant defense system might occur to counteract oxidant damage. Strikingly, we found positive correlation between some altered oxidative stress markers and disease severity, as determined by different clinical scales, with early-onset patients showing a more severe disturbance of the redox system than adult-onset patients. In summay, our results suggest that oxidative stress might contribute to SCA7 pathogenesis. Furthermore, oxidative stress biomarkers that were found relevant to SCA7 in this study could be useful to follow disease progression and monitor therapeutic intervention.

Rescue of impaired sociability and anxiety-like behavior in adult cacna1c-deficient mice by pharmacologically targeting eIF2α.

CACNA1C, encoding the Cav1.2 subunit of L-type Ca2+ channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1.2 signaling may contribute to neuropsychiatric-related disease symptoms via impaired PFC function. Here, we show that mice harboring loss of cacna1c in excitatory glutamatergic neurons of the forebrain (fbKO) that we have previously reported to exhibit anxiety-like behavior, displayed a social behavioral deficit and impaired learning and memory. Furthermore, focal knockdown of cacna1c in the adult PFC recapitulated the social deficit and elevated anxiety-like behavior, but not the deficits in learning and memory. Electrophysiological and molecular studies in the PFC of cacna1c fbKO mice revealed higher E/I ratio in layer 5 pyramidal neurons and lower general protein synthesis. This was concurrent with reduced activity of mTORC1 and its downstream mRNA translation initiation factors eIF4B and 4EBP1, as well as elevated phosphorylation of eIF2α, an inhibitor of mRNA translation. Remarkably, systemic treatment with ISRIB, a small molecule inhibitor that suppresses the effects of phosphorylated eIF2α on mRNA translation, was sufficient to reverse the social deficit and elevated anxiety-like behavior in adult cacna1c fbKO mice. ISRIB additionally normalized the lower protein synthesis and higher E/I ratio in the PFC. Thus this study identifies a novel Cav1.2 mechanism in neuropsychiatric-related endophenotypes and a potential future therapeutic target to explore.

[Is there a difference in the postoperative follow up of ureteropelvic junction obstruction according to age?] / ¿Existe diferencia en la evolución postoperatoria de la estenosis pieloureteral según la edad?

OBJECTIVE: To compare postoperative follow up in patients older and younger than 12 months who underwent surgical treatment of ureteropelvic junction obstruction (UJO). MATERIAL AND METHODS: Retrospective study of 77 patients, 78 kidney units, intervened from UJO (2007-2014). We analyzed epidemiological, clinical, echographic, and pre and postoperative renogram variables, outcomes and complications. We divided the patients into 2 groups according to age: group A ≤ 12 months and group B > 12 months, comparing the results by statistical analysis, considering p < 0.05 statistically significant. RESULTS: Group A: 38 patients, 26 males (68.4%), one bilateral UJO and 22 rights (57.9%), 36 prenatal diagnoses (92.3%) and mean age of intervention 5.28 months [range 0.24 -11,28]. We performed 9 minilumbotomies, 29 assisted by retroperitoneoscopy (ARP) and 1 pneumatic dilation (PD). Group B: 39 patients, 26 males (66.7%), 10 rights (25.64%), 19 prenatal diagnoses (48.7%) and mean age 6.13 years [range 1.13-14.52]. 15 minilumbotomies, 20 ARP, 3 laparoscopic and 1 PD. Preoperative mean renal function (MRF) of group A: 35.9 ± 13.4 [range 8-57] vs. 39.74 ± 13.91 [range 9-57] in group B (p = 0.347). Postoperative MRF 43.29 ± 18.2 [range 12-100] group A and 39.41 ± 12.89 [range 11-54] group B (p = 0.464). Group A and B: 11 and 8 complications, respectively (p = 0.429). We did not find statistically significant differences in the mean preoperative anteroposterior diameter (DAP) between both groups (p = 0.313). We compared DAP at 3, 6, 12, 24 and 48 postoperative months, observing a greater reduction of DAP from group A compared to B; however, we found only statistically significant differences in DAP at 3 months postoperatively (p = 0.047). CONCLUSION: Renal DAP is reduced postoperatively more in patients younger than 1 year. Moreover, an improvement of the DRF after pieloplasty can be observed despite not being statistically significant.

OBJETIVO: Comparar la evolución postquirúrgica en pacientes mayores y menores de 12 meses intervenidos de estenosis pieloureteral (EPU). MATERIAL Y METODOS: Estudio retrospectivo de 77 pacientes, 78 unidades renales, intervenidos por EPU (2007-2014). Analizamos variables epidemiológicas, clínicas, ecográficas y de renogramas pre y postoperatorios, resultados y complicaciones. Dividimos a los pacientes en 2 grupos según la edad: grupo A ≤ 12 meses y grupo B > 12 meses, comparando los resultados mediante análisis estadísticos (p < 0,05 estadísticamente significativo). RESULTADOS: Grupo A: 38 pacientes, 26 varones (68,4%), una EPU bilateral y 22 derechas (57,9%), 36 diagnósticos prenatales (92,3%) y edad media de intervención 5,28 meses [rango 0,24-11,28]. Realizamos 9 minilumbotomías, 29 asistidas por retroperitoneoscopia (ARP) y una dilatación neumática (DN). Grupo B: 39 pacientes, 26 varones (66,7%), 10 derechas (25,64%), 19 diagnósticos prenatales (48,7%) y edad media 6,13 años [rango 1,13-14,52]. Realizamos 15 minilumbotomías, 20 ARP, 3 laparoscópicas y 1 DN. Función renal diferencial media (FRDM) preoperatoria del grupo A: 35,9 ± 13,4 [rango 8-57] vs. 39,74 ± 13,91 [rango 9-57] grupo B (p = 0,347). FRDM postoperatoria 43,29 ± 18,2 [rango 12-100] grupo A y 39,41 ± 12,89 [rango 11-54] grupo B (p = 0,464). Grupos A y B: 11 y 8 complicaciones, respectivamente (p = 0,429). No encontramos diferencias estadísticamente significativas en la media del diámetro anteroposterior (DAP) de la pelvis preoperatoria entre ambos grupos (p = 0,313). Comparamos los DAP a los 3, 6, 12, 24 y 48 meses postoperatorios, observando una reducción mayor del DAP del grupo A frente al B, sin embargo, solo encontramos diferencias estadísticamente significativas en el DAP a los 3 meses postoperatorios (p = 0,047). CONCLUSION: El DAP de la pelvis renal se reduce más en los pacientes menores de 1 año a los 3 meses postoperatorios. Además, podemos observar una evidente mejoría de la FRDM tras la pieloplastia a pesar de no encontrar diferencias estadísticamente significativas.

Hip fracture registries: utility, description, and comparison.

Hip fractures (HF) are prevalent and involve high morbidity and mortality so improving their management is important. HF registries are a good way to improve knowledge about this condition and its quality of care, while at the same time reducing clinical variability, optimizing efficiency, improving outcomes, and reducing costs. INTRODUCTION: Hip fractures (HF) are a prevalent fragility fracture secondary to osteoporosis that involves high morbidity and mortality. They are low-impact fractures, resulting from a fall from a standing or sitting height. Despite numerous Clinical Practice Guidelines that establish uniform recommendations for their care, great variability persists regarding clinical and healthcare outcomes. Fracture registries can help detect deficits and establish measures to improve care. The objective of this work is to analyze the contents that a HF registry should have and to compare the characteristics of some national HF registries. METHODS: A literature search was conducted on several national hip fracture registries, and those that contain relevant information on the variables and their outcomes were selected. RESULTS: The selected HF registries were compared using the parameters they measure as well as the outcomes in the different countries. The variables collected in the majority of the databases and those that give useful information are as follows: sociodemographic variables (age, sex, place of residence), clinical variables (function before and after HF, anesthesia risk as measured by the ASA score, type of fracture, type of surgery and anesthesia, and in-hospital and 1-month mortality), and healthcare variables (pre-operative and overall stay, presence of collaboration with orthogeriatrics or with any clinician in addition to the surgeon, secondary prevention of new fractures by assessing the fall risk, and need for osteoporosis treatment). CONCLUSION: The recording of HF cases in different countries improves knowledge about handling this condition and its quality of care, while at the same time reducing clinical variability, optimizing efficiency, improving outcomes, and reducing costs. The debate on the variables that should be recorded is timely, such as organizing how to collect each measurement, and even trying to unify the national and international registries or using a current proposal such as the one from the Fragility Fracture Network.

Fetal laser ablation of feeding artery of cystic lung lesions with systemic arterial blood supply.

OBJECTIVE: To assess the effectiveness of laser surgery in fetuses with a cystic lung lesion with systemic arterial blood supply (hybrid lung lesion) at risk of perinatal death. METHODS: A cohort of five consecutive fetuses with a large hybrid lung lesion associated with hydrops and/or pleural effusion with severe lung compression was selected for percutaneous ultrasound-guided fetal laser ablation of the feeding artery (FLAFA) before 32 weeks' gestation in a single tertiary national referral center in Queretaro, Mexico. The primary outcomes were survival and need for postnatal surgery. RESULTS: FLAFA was performed successfully in all cases at a median gestational age of 24.9 (range, 24.4-31.7) weeks. After fetal intervention, dimensions in both lungs increased and fluid effusions resolved in all cases. All cases were delivered liveborn at term at a median gestational age of 39.6 (range, 38.0-39.7) weeks, without respiratory morbidity or need for oxygen support, resulting in perinatal survival of 100%. During follow-up, three (60%) cases showed progressive regression of the entire lung mass and did not require postnatal surgery, whereas in two (40%) cases a progressive decrease in size of the mass was observed but a cystic portion of the lung mass persisted and postnatal lobectomy was required. CONCLUSION: In fetuses with large hybrid lung lesions at risk of perinatal death, FLAFA is feasible and could improve survival and decrease the need for postnatal surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Effect of carbon sources on the growth and ethanol production of native yeast Pichia kudriavzevii ITV-S42 isolated from sweet sorghum juice.

The importance of non-Saccharomyces yeast species in fermentation processes is widely acknowledged. Within this group, Pichia kudriavzevii ITV-S42 yeast strain shows particularly desirable characteristics for ethanol production. Despite this fact, a thorough study of the metabolic and kinetic characteristics of this strain is currently unavailable. The aim of this work is to study the nutritional requirements of Pichia kudriavzevii ITV-S42 strain and the effect of different carbon sources on the growth and ethanol production. Results showed that glucose and fructose were both assimilated and fermented, achieving biomass and ethanol yields of 0.37 and 0.32 gg-1, respectively. Glycerol was assimilated but not fermented; achieving a biomass yield of 0.88 gg-1. Xylose and sucrose were not metabolized by the yeast strain. Finally, the use of a culture medium enriched with salts and yeast extract favored glucose consumption both for growth and ethanol production, improving ethanol tolerance reported for this genre (35 g L-1) to 90 g L-1 maximum ethanol concentration (over 100%). Furthermore Pichia kudriavzevii ITV-S42 maintained its fermentative capacity up to 200 g L-1 initial glucose, demonstrating that this yeast is osmotolerant.

[Psychoprophylaxis in elective paediatric general surgery: does audiovisual tools improve the perioperative anxiety in children and their families?] / Psicoprofilaxis quirurgica audiovisual en cirugía general pediátrica: ¿podemos disminuir la ansiedad del niño y de su familia?

AIM OF THE STUDY: Surgery is considered a stressful experience for children and their families who undergo elective procedures. Different tools have been developed to improve perioperative anxiety. Our objective is to demonstrate if the audiovisual psychoprophylaxis reduces anxiety linked to paediatric surgery. METHODS: A randomized prospective case-control study was carried out in children aged 4-15 who underwent surgery in a Paediatric Surgery Department. We excluded patients with surgical backgrounds, sever illness or non-elective procedures. Simple randomization was performed and cases watched a video before being admitted, under medical supervision. Trait and state anxiety levels were measured using the STAI-Y2, STAI-Y2, STAI-C tests and VAS in children under 6-years-old, at admission and discharge. RESULTS: 100 patients (50 cases/50 controls) were included, mean age at diagnosis was 7.98 and 7.32 respectively. Orchiopexy was the most frequent surgery performed in both groups. Anxiety state levels from parents were lower in the Cases Group (36.06 vs 39.93 p= 0.09 in fathers, 38.78 vs 40.34 p= 0.43 in mothers). At discharge, anxiety levels in children aged > 6 were statistically significant among cases (26.84 vs 32.96, p< 0.05). CONCLUSIONS: The use of audiovisual psychoprophylaxis tools shows a clinically relevant improvement in perioperative anxiety, both in children and their parents. Our results are similar to those reported by other authors supporting these tools as beneficial strategy for the family.

OBJETIVOS: La cirugía supone una experiencia traumática tanto para el niño como para su familia. Recientemente se han diseñado estrategias audiovisuales en nuestro Servicio para tratar de disminuir la ansiedad vinculada a la intervención quirúrgica. Nuestro objetivo es analizar si la psicoprofilaxis audiovisual reduce los niveles de ansiedad derivados del evento quirúrgico. MATERIAL Y METODOS: Estudio prospectivo aleatorizado en niños intervenidos en el Servicio de Cirugía Pediátrica (4-15 años). Se excluyeron pacientes con antecedentes quirúrgicos, patología grave o procedimientos de Urgencia. La aleatorización en casos-controles fue realizada mediante sistema par-impar. Los casos visualizaron el vídeo antes del ingreso bajo supervisión médica. Se realizó la evaluación de los niveles de ansiedad estado y ansiedad rasgo mediante test autocompletables (STAI-Y1,STAI-Y2,STAI-C, test EVA en < 6 años) al ingreso y al alta en ambos grupos. RESULTADOS: 100 pacientes fueron incluidos (50 casos/50 controles) edad media de 7,98 y 7,32 años, respectivamente. La intervención practicada con mayor frecuencia fue la orquidopexia en ambos grupos. Se observaron niveles de ansiedad estado menores en los progenitores de los casos frente a los controles (36,06 vs 39.93 en padres p= 0,09, 38,78 vs 40,34 en madres p= 0,43). Al alta, los niveles de ansiedad fueron menores en niños > 6 años (26,84 vs 32,96), siendo esta diferencia estadísticamente significativa (p< 0,05). CONCLUSIONES: El uso de la psicoprofilaxis prequirúrgica mediante herramientas audiovisuales disminuye la ansiedad de forma clínicamente relevante tanto en los niños como en sus familias de manera sencilla y fácilmente reproducible. Nuestros resultados coinciden con los reportados en la literatura y consideramos esta herramienta beneficiosa para el núcleo familiar.

[Analysis of hypertrophic pyloric stenosis: size does matter]. / Análisis de la estenosis hipertrófica del píloro: el tamaño sí importa.

OBJECTIVES: To analyze the correlation between pyloric size and evolution of patients surgically treated for infantile hypertrophic pyloric stenosis (IHPS). PATIENTS AND METHODS: We realized a retrospective study of 109 patients undergoing IHPS in 5 years. We analyzed by χ2 test if a correlation between evolution time, age and postoperative vomiting and gastroesophageal reflux disease (GERD), and pyloric muscle thickness (group A > 4.5 mm and group B ≤ 4.5 mm) and pyloric channel length (group A ≥ 20 mm and group B < 20 mm) exists. RESULTS: There is a statistically significant correlation between longer evolution history (>48 h) and pyloric length ≥ 20 mm and between age (> 30 days) and muscle thickness > 4.5 mm (p= 0.022 and p= 0.009, respectively). Also, 38.5% of 109 patients had postoperative emesis 2 days after surgery and 13.8% had GERD for a median time of 8.27 months (1-12 months), showing that there is a statistically significant correlation (p= 0.007) between pyloric channel length ≥ 20 mm and postoperative emesis. It was not observed correlation between pyloric thickness and length and GERD. CONCLUSIONS: It has been observed that there is correlation between pyloric length ≥ 20 mm and postoperative emesis. However, it has not been observed regarding the pyloric muscle thickness. A longer preoperative evolution and age > 30 days are correlated to channel length ≥ 20 mm and muscle thickness > 4.5 mm, respectively.

OBJETIVOS: Analizar la relación entre el tamaño del píloro y la evolución de los pacientes intervenidos de estenosis hipertrófica del píloro (EHP). PACIENTES Y METODOS: Estudio retrospectivo de 109 pacientes intervenidos de EHP en 5 años. Se analiza mediante el test de ji al cuadrado si existe relación entre las horas de evolución, la edad y los vómitos y reflujo gastroesofágico (RGE) postoperatorios, con el grosor muscular pilórico (grupo A > 4,5 mm y grupo B ≤ 4,5 mm) y la longitud del canal pilórico (grupo A ≥ 20 mm y grupo B < 20 mm). RESULTADOS: Existe una relación estadísticamente significativa entre el mayor tiempo de evolución (> 48 h) y la longitud del píloro ≥ 20 mm y entre la edad (> 30 días) y el grosor muscular > 4,5 mm, con una p= 0,022 y p= 0,009, respectivamente. Asimismo, de los 109 pacientes, el 38,5% presentó algún vómito durante los 2 días posteriores a la intervención y el 13,8% presentó RGE durante un tiempo medio de 8,27 meses (1-12 meses), demostrándose que existe relación entre una longitud pilórica ≥ 20 mm y la presencia de vómitos postoperatorios, siendo estadísticamente significativo (p= 0,007). No encontramos una relación estadísticamente significativa entre el grosor y la longitud del píloro con el RGE. CONCLUSIONES: Se ha observado que existe relación entre una longitud del canal pilórico ≥ 20 mm y los vómitos postoperatorios, sin embargo, no se ha observado relación con el grosor muscular pilórico. Pese a ello, un mayor tiempo de evolución y una edad > 30 días sí están relacionados con la longitud ≥ 20 mm y el grosor muscular > 4,5 mm, respectivamente.

[Functional outcomes in postsurgery for Hirschsprung´s disease]. / Resultados funcionales en postoperados de enfermedad de Hirschsprung.

OBJECTIVE: To analyze functional outcomes of patients operated for Hirschsprung's disease (HD). METHODS AND MATERIAL: Retrospective study of patients with HD (2000-2014). We analyzed surgical technique, age at diagnostic and treatment, amount of resected bowel, complications and their influence on functional outcomes. RESULTS: Of the 44 diagnosed with HD, 37 were operated in our center. Men 29 (78.4%). With associated pathology 7 (18.9%), and 5 (13.5%) made their debut with enterocolitis. Diagnostic average age 1.04 (0.0 to 7.1 years) and operation average age 1.4 (0.3 to 9.3 years). We did transanal endorectal pull-through (TERPT) in 17 (45.9%) patients and transabdominal approach (TAB) in 20 (54.1%). Received postoperative dilations 8 (21.6%) patients. Functional outcomes were evaluated at an average age of 9.6 (4.7-15.7years) incontinence/soiling were found in 6/28 (21.4%) and constipation in 5/28 (17.9%). The highest rate of incontinence/ soiling was present in 41.7 % TERPT vs. 6.2% TAB (p= 0,036). However, the average age at follow-up in patients with incontinence/soiling was 5.9 ± 1.3 years old, less than the 10,6 ± 3.2 years in the ones without incontinence/soiling (p< 0,001). We found that the 5 cases of constipation arose in patients with TAB (p= 0, 044), and likewise all were operated under 1 year of age. CONCLUSION: Despite the well known benefits of the TERPT over the TAB, we found a greater degree of incontinence/soiling in the TERPT, which could be explained by a less follow up, since incontinence/soiling improves with age. On the other hand there is a higher rate of constipation in the TAB that lasts in time.

OBJETIVO: Analizar resultados funcionales de pacientes operados por enfermedad de Hirschsprung (EH). MATERIAL Y METODOS: Estudio retrospectivo de pacientes con EH (2000-2014). Se analizó técnica quirúrgica, edad diagnóstica y de tratamiento, cantidad de intestino resecado, complicaciones y su influencia sobre resultados funcionales. RESULTADOS: De los 44 diagnosticados con EH se operaron en nuestro centro 37. Varones 29 (78,4%). Con patología asociada 7 (18,9%), y 5 (13,5%) debutaron con enterocolitis. Edad media diagnóstica 1,04 (rango: 0,01-7,1 años) y de intervención 1,4 (0,3-9,3 años). A 17 (45,9%) se realizó descenso endorectal trans-anal (DERTA) y a 20 (54,1%) descenso trans-abdominal (DTA). Recibieron dilataciones postquirúrgicas 8 (21,6%). Los resultados funcionales se valoraron a una edad media de 9,6 (4,7-15,7 años) encontrando incontinencia/encopresis en 6/28 (21,4%) y estreñimiento en 5/28 (17,9%). El mayor índice de incontinencia/encopresis se presentó en los DERTA 41,7% vs 6,2% DTA (p= 0,036); sin embargo, la edad media al seguimiento en pacientes con incontinencia/encopresis fue menor 5,9 ± 1,3 años vs 10,6 ± 3,2 años en los que no la presentan (p< 0,001). Encontramos que los 5 casos de estreñimiento se presentaron en pacientes con DTA (p= 0,044) y, así mismo, todos operados ≤ 1 año de edad. CONCLUSIONES: A pesar de los ya comprobados beneficios del DERTA sobre el DTA, hemos encontrado un mayor grado de incontinencia/encopresis en el DERTA, que podría estar explicado por el menor tiempo de seguimiento, dado que la incontinencia/encopresis mejora con la edad. Por el contrario, hay un mayor índice de estreñimiento en el DTA que se prolonga en el tiempo.

[The diagnosis of pilomatrixoma in children is not as easy as it may seem. A review of 126 cases]. / El diagnóstico del pilomatrixoma infantil no es tan fácil como parece: revisión de 126 casos.

OBJECTIVE: To describe our experience with pilomatrixomas, clinical presentation, clinical accuracy, associated diseases, and surgical treatment. METHODS: A retrospective review of patients with a pathology report of an excised pilomatrixoma between 2011 and 2014. Data regarding gender, age of intervention, number of masses, size, location, and preoperative clinical diagnosis, pathology report, recurrences, and associated diseases were collected. Statistical analysis was performed using EPIinfo 7.1.5. RESULTS: A total of 151 tumors in 138 patients were removed, 25 were excluded for having a clinical diagnosis of pilomatrixoma without confirmation of the pathology report. The remaining 126 cases have an average age of 8.26 years (range 1-14 years) and 50.72% are males. The tumors were located above the umbilicus in 97% of the cases, with a higher concentration of 50.72% in the head and neck. The clinical diagnosis corresponds with the pathology report in 69.05% of cases. Out of these confirmed cases the most frequent differential diagnosis is cystic lesion (11.90%) and dermoid cyst (10.22%). There were no cases of malignant degeneration. The average diameter is 1.13 cm, there were no recurrences, but there were 11 cases of a new lesion in a different location. There is no statistical association with other pathologies. The most frequent diseases found were obesity (3.62%) and attention deficit syndrome (3.62%). CONCLUSION: The pilomatrixoma is a tumor that appears predominantly in the head and neck, and has a difficult clinical diagnosis. Complete removal is curative, although it does not prevent the appearance of new lesions.

OBJETIVO: Describir nuestra experiencia con pilomatrixomas, examinando la presentación clínica, acierto clínico, enfermedades asociadas y tratamiento quirúrgico. MATERIAL Y METODOS: Estudio retrospectivo de los pacientes con diagnóstico anatomo-patológico (AP) de pilomatrixoma, en el periodo de 2011 a 2014. Se recopilaron datos sobre genero, edad de intervención, número de tumoraciones, tamaño, localización, diagnóstico preoperatorio, anatomía patológica, reintervenciones y patología asociada. Se realizó el análisis estadístico con EPIinfo 7.1.5. RESULTADOS: Se extirparon un total de 151 tumores en 138 pacientes, excluyendo 25 tumoraciones por tener diagnóstico clínico de pilomatrixoma sin confirmación patológica. Los 126 casos que tienen confirmación AP de pilomatrixoma tienen una edad media de exéresis de 8,26 años de edad (1-14 años) y el 50,72% son del género masculino. El 97% de los tumores se localizan por encima del ombligo, concentrándose en la cabeza y cuello el 52,9%. La sospecha clínica corresponde con AP en el 69,05%. De los casos confirmados, los diagnósticos clínicos diferenciales más frecuentes son lesión quística (11,90%) y quiste dermoide (10,22%); no hubo pilomatrixomas con degeneración maligna. La media de diámetro es de 1,13 cm, no hubo recidivas locales, pero sí 11 nuevos casos de pilomatrixomas en otra localización. No hay asociación estadísticamente significativa a otras patologías. Las enfermedades más frecuentes encontradas son la obesidad (3,62%) y el síndrome de déficit de atención (3,62%). CONCLUSION: El pilomatrixoma es una tumoración predominantemente de aparición en cara y cuello, de difícil diagnóstico clínico. La exéresis completa es curativa, aunque no previene la aparición de nuevas lesiones.

[Is there an ideal patient for transumbilical laparoscopic assisted appendectomy?] / ¿Existe el paciente ideal para la apendicectomía transumbilical asistida por laparoscopia?

OBJECTIVES: To identify the factors that lead to postoperative morbidity in acute appendicitis patients treated using a TULAA (Transumbilical laparoscopic assisted appendectomy) approach. MATERIAL AND METHODS: Retrospective review of patients treated through a TULAA approach between 2007 and 2014. Data concerning the location of the appendix, need for conversion, appendiceal abscess or perforation, surgical time and other complications were collected. Student's T test and Chi-squared test were used for statistical analysis. RESULTS: A total of 111 appendectomies underwent TULAA. The average operating time was 79 minutes (45-150). Nonperforated appendicitis was found in 90% of patients with 10% having perforated appendicitis or appendiceal abscess. In 35,13% of cases, additional trocars were used, usually when the appendix was in a retrocecal position (89,5%). When the appendix was found in a pelvic or ileal position, a need for extra trocars decreased to 25.9% (p< 0.05). The surgery was converted to open surgery in 6,3% of the cases. The appendix in a retrocecal position had a conversion rate of 20,8% compared to 2,3% of cases with an appendix in a pelvic location (p< 0.05). A total of 3,6% reported postoperative wound infection, possibly caused by perforation of the appendix during extraction (p< 0.05). All the perforated appendixes were considered complicated appendixes. CONCLUSIONS: The retrocecal location of the appendix is associated with the need to install additional trocars or conversion to open surgery. The TULAA approach is ideal for patients with nonperforated acute appendicitis in a pelvic or ileal location.

OBJETIVOS: Identificar los factores que influyen en la morbilidad postoperatoria en pacientes intervenidos mediante apendicectomía transumbilical asistida por laparoscopia o TULAA (transumbilical laparoscopic assisted appendectomy). MATERIAL Y METODOS: Estudio analítico retrospectivo de pacientes intervenidos mediante TULAA en nuestro centro entre 2007-2014. Se incluyeron las variables: localización del apéndice, reconversiones, tipo de apendicitis, tiempo quirúrgico y complicaciones. Se utilizó t de Student y chi-cuadrado para el análisis estadístico. RESULTADOS: Se analizaron un total de 111 apendicectomías TULAA. Tiempo quirúrgico medio 79 minutos (45-150). El 90% de pacientes tenían apendicitis simple y 10% apendicitis complicada. En 35,13% casos se utilizaron trócares adicionales, cuando el apéndice se posicionaba de forma atípica ascendió al 89,5% de casos, mientras que cuando el apéndice se encontró en posición típica este dato disminuía al 25,9% (p< 0,05). Se reconvirtió en un 6,3% de casos (20,8% apéndice en posición atípica, 2,3% apéndice en posición habitual, pp< 0,05). Se encontró un 3,6% de casos con infección de herida quirúrgica explicada por perforación iatrogénica en la maniobra de extracción del apéndice (pp< 0,05). Todas las apéndices perforadas en la maniobra de extracción se trataron de apendicitis complicadas. CONCLUSIONES: La posición anómala del apéndice se relaciona de forma significativa con la necesidad de colocación de trócares adicionales o reconversión a cirugía abierta. Consideramos la TULAA ideal en los casos de localización anterior del apéndice y en apendicitis no complicadas.