Reliability of different body temperature measurement sites during normothermic cardiac surgery.

INTRODUCTION: Patients undergoing cardiac surgery can experience significant thermal changes during the perioperative period and, for that reason, it is essential to monitor temperatures with adequate accuracy and precision during cardiopulmonary bypass (CPB). The primary aim of the current study was to measure the discrepancies between temperatures at different body sites during normothermic or mild hypothermic CPB. METHODS: 48 patients undergoing cardiac surgery participated in our study. Simultaneous temperatures were measured at nasopharynx, pulmonary artery, arterial outlet, venous inlet, forehead using a heat flux sensor, and urinary bladder at 5-min intervals throughout surgery. The Bland-Altman plot for repeated measures was used to assess concordance between methods. RESULTS: The duration of surgery was 360 min (interquartile range (IQR) 300-412), while the median cross-clamp time was 135 min (IQR 101-169). During the CPB time, the average difference between arterial outlet and nasopharyngeal temperature was -0.16°C (95% limits of agreement of ±0.93). The bias between arterial outlet and the venous inflow was 0.16°C and the 95% limits of agreement were -0.63 to 0.95°C. The Bland-Altman analysis showed an average difference between oxigenator arterial outlet and bladder probe of -0.62 (95% limits of agreement of ±1.3). The average difference between arterial outlet and Tcore™ temperatures was 0.08°C (95% limits of agreement of ±1.46). 25 patients (52.08%) presented nasopharyngeal temperatures higher than 37°C in the post-CPB period, but none of them exceeded 38°C. CONCLUSIONS: Perfusionists should be cautious when using the nasopharyngeal site as the only surrogate of brain temperature, even in normothermic cardiac surgery because the precision of measurements is not entirely adequate.

The age again in the eye of the COVID-19 storm: evidence-based decision making.

BACKGROUND: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. RESULTS: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/µL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. CONCLUSION: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.

COVID-19: age, Interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study.

BACKGROUND: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. RESULTS: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. CONCLUSIONS: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.

Bilateral Adrenalectomy in a Patient With Refractory Primary Aldosteronism Due to Adrenal Hyperplasia.

Primary aldosteronism (PA) is a frequent cause of secondary hypertension. The main cause of PA is bilateral adrenal hyperplasia, and treatment is usually medical with mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone. In this paper, we present a rare clinical case of a middle-aged female with refractory arterial hypertension and hypokalemia that complementary medical tests confirmed PA due to bilateral hyperplasia, and despite a maximum dose of spironolactone and oral potassium supplements, there was no clinical response. Because of this, finally, the patient needed surgical treatment based on bilateral adrenalectomy, which was effective. This is unusual and poorly described in the medical literature.

Safety of Positive Pressure Extubation Technique.

BACKGROUND: Laboratory studies suggest applying positive pressure without endotracheal suction during cuff deflation and extubation. Although some studies reported better physiological outcomes (e.g. arterial blood gases) with this technique, the safety of positive pressure extubation technique has not been well studied. The aim of this study was to determine the safety of the positive-pressure extubation technique compared with the traditional extubation technique in terms of incidence of complications. METHODS: Adult subjects who were critically ill and on invasive mechanical ventilation who met extubation criteria were included. The subjects were randomly assigned to positive-pressure extubation (n = 120) or to traditional extubation (n = 120). Sequential tests for noninferiority and, when appropriate, for superiority were performed. Positive pressure was considered noninferior if the upper limit of the CI for the absolute risk difference did not exceed a threshold of 15% in favor of the traditional group, both in per protocol and intention-to-treat analyses. A P value of <.05 was considered significant. RESULTS: A total of 236 subjects were included in the primary analysis (per protocol) (119 in the positive-pressure group and 117 in the traditional group). The incidence of overall major and minor complications, pneumonia, extubation failure, and reintubation was lower in the positive-pressure group than in the traditional group, with statistical significance for noninferiority both in the per protocol (P < .001) and intention-to-treat (P < .001) analyses. The lower incidence of major complications found in the positive-pressure group reached statistical significance for the superiority comparison, both in per protocol (P = .03) and intention-to-treat (P = .049) analyses. No statistically significant differences were found in the superiority comparison for overall complications, minor complications, pneumonia, extubation failure, and reintubation. CONCLUSIONS: Positive pressure was safe and noninferior to traditional extubation methods. Furthermore, positive pressure has shown to be superior in terms of a lower incidence of major complications. (ClinicalTrials.gov registration NCT03174509.).

Spontaneous human adult stem cell transformation.

Human adult stem cells are being evaluated widely for various therapeutic approaches. Several recent clinical trials have reported their safety, showing them to be highly resistant to transformation. The clear similarities between stem cell and cancer stem cell genetic programs are nonetheless the basis of a recent proposal that some cancer stem cells could derive from human adult stem cells. Here we show that although they can be managed safely during the standard ex vivo expansion period (6-8 weeks), human mesenchymal stem cells can undergo spontaneous transformation following long-term in vitro culture (4-5 months). This is the first report of spontaneous transformation of human adult stem cells, supporting the hypothesis of cancer stem cell origin. Our findings indicate the importance of biosafety studies of mesenchymal stem cell biology to efficiently exploit their full clinical therapeutic potential.

Tempering Proactive Cognitive Control by Transcranial Direct Current Stimulation of the Right (but Not the Left) Lateral Prefrontal Cortex.

Behavioral and neuroimaging data support the distinction of two different modes of cognitive control: proactive, which involves the active and sustained maintenance of task-relevant information to bias behavior in accordance with internal goals; and reactive, which entails the detection and resolution of interference at the time it occurs. Both control modes may be flexibly deployed depending on a variety of conditions (i.e., age, brain alterations, motivational factors, prior experience). Critically, and in line with specific predictions derived from the dual mechanisms of control account (Braver, 2012), findings from neuroimaging studies indicate that the same lateral prefrontal regions (i.e., left dorsolateral cortex and right inferior frontal junction) may implement different control modes on the basis of temporal dynamics of activity, which would be modulated in response to external or internal conditions. In the present study, we aimed to explore whether transcraneal direct current stimulation over either the left dorsolateral prefrontal cortex or the right inferior frontal junction would differentially modulate performance on the AX-CPT, a well-validated task that provides sensitive and reliable behavioral indices of proactive/reactive control. The study comprised six conditions of real stimulation [3 (site: left dorsolateral, right dorsolateral and right inferior frontal junction) × 2 (polarity: anodal and cathodal)], and one sham condition. The reference electrode was always placed extracephalically. Performance on the AX-CPT was assessed through two blocks of trials. The first block took place while stimulation was being delivered, whereas the second block was administered after stimulation completion. The results indicate that both offline cathodal stimulation of the right dorsolateral prefrontal cortex and online anodal stimulation of the right inferior frontal junction led participants to be much less proactive, with such a dissociation suggesting that both prefrontal regions differentially contribute to the adjustment of cognitive control modes. tDCS of the left-DLPFC failed to modulate cognitive control. These results partially support the predictions derived from the dual mechanisms of control account.

Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using CRISPR/Cas9.

Efficient methodologies for recreating cancer-associated chromosome translocations are in high demand as tools for investigating how such events initiate cancer. The CRISPR/Cas9 system has been used to reconstruct the genetics of these complex rearrangements at native loci while maintaining the architecture and regulatory elements. However, the CRISPR system remains inefficient in human stem cells. Here, we compared three strategies aimed at enhancing the efficiency of the CRISPR-mediated t(11;22) translocation in human stem cells, including mesenchymal and induced pluripotent stem cells: (1) using end-joining DNA processing factors involved in repair mechanisms, or (2) ssODNs to guide the ligation of the double-strand break ends generated by CRISPR/Cas9; and (3) all-in-one plasmid or ribonucleoprotein complex-based approaches. We report that the generation of targeted t(11;22) is significantly increased by using a combination of ribonucleoprotein complexes and ssODNs. The CRISPR/Cas9-mediated generation of targeted t(11;22) in human stem cells opens up new avenues in modeling Ewing sarcoma.

Identification of recurrent chromosomal breakpoints in multiple myeloma with complex karyotypes by combined G-banding, spectral karyotyping, and fluorescence in situ hybridization analyses.

The description of novel chromosomal aberrations in multiple myeloma (MM) remains necessary to fully understand the pathogenesis of this heterogeneous disease. Therefore, we have used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) with locus-specific probes to characterize the chromosomal abnormalities in 11 MM cases in which G-banding revealed a complex karyotype. SKY refined G-banding karyotypes in all cases. Recurrent breakpoints involved bands Xp11, 8q24, 11q13, 12q13, 13q21, and 14q32. In addition, combined SKY and FISH analyses permitted us to identify a subset of patients harboring 22q11.2 rearrangements not involving the IGL locus. This finding suggests the presence of other gene(s) in band 22q11 that might be implicated in MM pathogenesis. Moreover, band 1p13 was identified as a novel partner of immunoglobulin (IG) translocations in MM. Finally, using interphase FISH, we have detected interstitial deletions in 13q14 and 17p13, as well as cryptic translocations affecting IGH, which were neither detected by G-banding nor by SKY. The results of the present study suggest the existence of hitherto unknown nonrandom chromosomal changes that may play a role in the pathogenesis of MM. Our findings underline the importance of the combination of banding, SKY, and FISH analyses to increase the accuracy of karyotype interpretation in plasma cell neoplasias.

The impact of social factors on human immunodeficiency virus and hepatitis C virus co-infection in a minority region of Si-chuan, the People's Republic of China: a population-based survey and testing study.

BACKGROUND: While many human immunodeficiency virus (HIV) studies have been performed in Liangshan, most were focused only on HIV infection and based on a sampling survey. In order to fully understand HIV and hepatitis C virus (HCV) prevalence and related risk factors in this region, this study implemented in 2009, included a survey, physical examination, HIV and HCV test in two towns. METHODS: All residents in two towns of the Butuo county were provided a physical examination and blood tests for HIV and HCV, and then followed by an interview for questionnaire. RESULTS: In total, 10,104 residents (92.4%) were enrolled and 9,179 blood samples were collected for HIV and HCV testing, 6,072 were from individuals >14 years old. The rates of HIV, HCV, and HIV/HCV co-infection were 11.4%, 14.0%, and 7.7%, respectively for >14-year-old residents. The 25-34 yr age group had the highest prevalence of HIV, HCV, and HIV/HCV co-infections, reaching 24.4%, 26.2% and 16.0%, respectively. Overall, males had a much higher prevalence of all infections than females (HIV: 16.3% vs. 6.8%, HCV: 24.6% vs. 3.9%, HIV/HCV co-infected: 14.7% vs. 1.1%, respectively; P = 0.000). Approximately half of intravenous drug users tested positive for HIV (48.7%) and 68.4% tested positive for HCV. Logistic regression analysis showed that five factors were significantly associated with HIV and HCV infection: gender (odds ratio [OR]  = 5.8), education (OR = 2.29); occupation (student as reference; farmer: OR = 5.02, migrant worker: OR = 6.12); drug abuse (OR = 18.0); and multiple sexual partners (OR = 2.92). Knowledge of HIV was not associated with infection. CONCLUSION: HIV and HCV prevalence in the Liangshan region is very serious and drug use, multiple sexual partners, and low education levels were the three main risk factors. The government should focus on improving education and personal health awareness while enhancing drug control programs.

Ovariectomy increases the participation of hyperpolarizing mechanisms in the relaxation of rat aorta.

This study examines the downstream NO release pathway and the contribution of different vasodilator mediators in the acetylcholine-induced response in rat aorta 5-months after the loss of ovarian function. Aortic segments from ovariectomized and control female Sprague-Dawley rats were used to measure: the levels of superoxide anion, the superoxide dismutases (SODs) activity, the cGMP formation, the cGMP-dependent protein kinase (PKG) activity and the involvement of NO, cGMP, hydrogen peroxide and hyperpolarizing mechanisms in the ACh-induced relaxation. The results showed that ovariectomy did not alter ACh-induced relaxation; incubation with L-NAME, a NO synthase inhibitor, decreased the ACh-induced response to a lesser extent in aorta from ovariectomized than from control rats, while ODQ, a guanylate cyclase inhibitor, decreased that response to a similar extent; the blockade of hyperpolarizing mechanisms, by precontracting arteries with KCl, decreased the ACh-induced response to a greater extent in aortas from ovariectomized than those from control rats; catalase, that decomposes hydrogen peroxide, decreased the ACh-induced response only in aorta from ovariectomized rats. In addition, ovariectomy increased superoxide anion levels and SODs activity, decreased cGMP formation and increased PKG activity. Despite the increased superoxide anion and decreased cGMP in aorta from ovariectomized rats, ACh-induced relaxation is maintained by the existence of hyperpolarizing mechanisms in which hydrogen peroxide participates. The greater contribution of hydrogen peroxide in ACh-induced relaxation is due to increased SOD activity, in an attempt to compensate for increased superoxide anion formation. Increased PKG activity could represent a redundant mechanism to ensure vasodilator function in the aorta of ovariectomized rats.

The differential tissue expression of inflammatory, oxidative stress, and apoptosis markers in human uncontrolled non-heart-beating donors.

BACKGROUND: Uncontrolled non-heart-beating donor (UNHBD) transplantation offers a major opportunity to ameliorate the effects of the donor shortage. However, little is known about the true status of the organs obtained from these donors. UNHBD transplantation is performed under unfavorable conditions and involves exposure to several harmful stimuli that have been identified as triggers for immediate inflammatory response, oxidative stress, and apoptotic phenomena. This adverse scenario could explain the higher rates of graft dysfunction due to primary nonfunction traditionally observed in NHBD. Our aim was to assess the expression of proinflammatory, oxidative, and apoptotic markers in liver, lung, and pancreas tissue samples obtained from UNHBD and to compare these expression levels with those observed in brain-dead donors (BDD). METHODS: Samples from human type 2 NHBD and BDD were obtained at the end of cold storage. Interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-10, endothelial nitric oxide synthase, inducible nitric oxide synthase, type 1 heme oxygenase, type 2 heme oxygenase, Bax, and Bcl-2 protein and mRNA expression, as well as catalase, glutathione peroxidase, and glutathione reductase tissue activity, were determined. RESULTS: UNHBD showed similar or lower expression of proinflammatory mediators and apoptosis markers in all three organs without modifications to the anti-inflammatory cytokines. Although the major oxidative stress marker levels were also comparable in both types of donors, the type 1 heme oxygenase mRNA expression and antioxidant enzyme activity were slightly diminished in UNHBD. CONCLUSIONS: The initial tissue damage generated during the UNHB donation process is at least comparable with that observed in BDD. However, although the expression of the immediate immune response and apoptosis markers is similar, a mild impairment of the local antioxidant activity was observed.

FcRL3 gene promoter variant is associated with peripheral arthritis in Crohn's disease.

BACKGROUND: The mechanisms responsible for the pathogenesis of peripheral arthropathies (PA) in Crohn's disease (CD) are largely unknown, although many studies indicate that genetic and environmental factors are likely to contribute to risk. METHODS: Because variants in the Fc receptor-like 3 (FcRL3) gene have recently been associated with rheumatoid arthritis and several other autoimmune diseases, we tested 2 FcRL3 promoter variants (-169 C>T and -110 G>A) for association with PA in Spanish CD patients that were recruited from a single center and followed for at least 4 years (mean follow-up time, 11 years). RESULTS: Among the 342 CD patients evaluated, there were 88 cases of peripheral arthropathy; 31 were classified as arthritis and 57 were classified as arthralgia. We used contingency tables and logistic regression to test for association between PA or either subtype and FcRL3 and other factors that have previously been associated with extraintestinal manifestations in CD. CONCLUSIONS: We found that female sex, colonic involvement, and the AA genotype at -110 G>A were associated with increased risk of both subtypes of PA, although the association appears to be stronger for arthritis than for arthralgia.

Heridas cardíacas: utilidad de la ecografía en su diagnóstico / Cardiac wounds: surgeon-performed ultrasound for diagnostic procedure

Introducción: En muchos centros dedicados a la atención del trauma la ecografía ha pasado a formar parte, en forma sistemática, de la evaluación inicial de los pacientes con traumatismos toracoabdominales. Objetivos: Evaluar la utilidad de la ecografía realizada por el cirujano para certificar o descartar la presencia de un hemopericardio en las heridas torácicas. Lugar de aplicación: Hospital Donación Francisco Santojanni y Hospital José Equiza (González Catán). Diseño: Estudio observacional prospectivo. Población: Se estudiaron ecográficamente 29 pacientes con heridas en el área cardíaca o con heridas de proyectil que interesaban ambos hemitórax. Se incluyó una paciente con un hemipericardio a consecuencia de un cateterismo cardíaco. Resultados: No falleció ningún paciente. Presentaban hemopericardio traumático 3 (10,3 por ciento) de los 29 pacientes estudiados: verdaderos positivos 3; verdaderos negativos 26; falsos positivos 0; falsos negativos 0; sensibilidad 100 por ciento; especificidad 100 por ciento. Conclusiones: Basados en una revisión de la bibliografía sobre el tema y en nuestra experiencia consideramos que la ecografía, en pacientes con posibles heridas cardíacas, es un procedimiento de diagnóstico no invasivo, altamente sensible y específico, económico, rápido, repetible y que puede ser realizado e interpretado por un cirujano convenientemente entrenado