Replication study on the role of dopamine-dependent prefrontal reactivations in human extinction memory retrieval.

Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In a previous study, we found that post-extinction L-DOPA administration improved extinction memory retrieval 24 h later. Furthermore, spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predicted extinction memory retrieval, L-DOPA increased the number of these reactivations, and this mediated the effect of L-DOPA on extinction memory retrieval. Here, we conducted a preregistered replication study of this work in healthy male participants. We confirm that spontaneous post-extinction vmPFC reactivations predict extinction memory retrieval. This predictive effect, however, was only observed 90 min after extinction, and was not statistically significant at 45 min as in the discovery study. In contrast to our previous study, we find no evidence that L-DOPA administration significantly enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity. Further, trait salivary alpha-amylase negatively predicts retrieval, and this effect is reduced by L-DOPA treatment. Importantly, the latter findings result from non-preregistered analyses and thus further investigation is needed.

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves.

BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

Characterization of hypersensitivity reactions to polysulfone hemodialysis membranes.

BACKGROUND: In recent years, cases have been reported in which unexpected systemic hypersensitivity reactions occurred in patients dialyzed with polysulfone- or polyethersulfone-biocompatible membranes in the absence of other risk factors. The pathomechanisms involved in these reactions are largely unknown. OBJECTIVE: To characterize hypersensitivity reactions to polysulfone hemodialysis using clinical and laboratory data and to identify biomarkers suitable for endotype identification and diagnosis. METHODS: We prospectively collected data from 29 patients with suspected hypersensitivity reactions to polysulfone hemodialysis membranes. Clinical laboratory parameters such as tryptase, blood cell counts, and complement levels were recorded. Acute samples were obtained from 18 cases for the ex vivo assessment of basophil activation by flow cytometry analysis of CD63, CD203, and FcεRI cell membrane expression. Serum cytokines and anaphylatoxin concentrations were evaluated in 16 cases by Luminex and cytometric bead array analysis. RESULTS: Tryptase was elevated during the acute reaction in 4 cases. Evidence of basophil activation was obtained in 10 patients. Complement activation was found in only 2 cases. However, C5a serum levels tended to increase during the acute reaction in those patients with hypoxemia. Significantly higher serum levels of interleukin-6 were observed during the acute reactions to polysulfone hemodialysis (P = .0103). CONCLUSION: Based on biomarker analysis, various endotypes were identified, including type I-like (with the involvement of mast cells or basophils), complement, and cytokine (interleukin-6) release-related reactions, with some patients showing mixed reactions. Further research is needed to unravel the exact mechanisms involved in the activation of these cellular and molecular pathways.

Development of multisensory integration following prolonged early-onset visual deprivation.

Adult humans make effortless use of multisensory signals and typically integrate them in an optimal fashion.1 This remarkable ability takes many years for normally sighted children to develop.2,3 Would individuals born blind or with extremely low vision still be able to develop multisensory integration later in life when surgically treated for sight restoration? Late acquisition of such capability would be a vivid example of the brain's ability to retain high levels of plasticity. We studied the development of multisensory integration in individuals suffering from congenital dense bilateral cataract, surgically treated years after birth. We assessed cataract-treated individuals' reliance on their restored visual abilities when estimating the size of an object simultaneously explored by touch. Within weeks to months after surgery, when combining information from vision and touch, they developed a multisensory weighting behavior similar to matched typically sighted controls. Next, we tested whether cataract-treated individuals benefited from integrating vision with touch by increasing the precision of size estimates, as it occurs when integrating signals in a statistically optimal fashion.1 For participants retested multiple times, such a benefit developed within months after surgery to levels of precision indistinguishable from optimal behavior. To summarize, the development of multisensory integration does not merely depend on age, but requires extensive multisensory experience with the world, rendered possible by the improved post-surgical visual acuity. We conclude that early exposure to multisensory signals is not essential for the development of multisensory integration, which can still be acquired even after many years of visual deprivation.

Reduced Efficacy of d-Amphetamine and 3,4-Methylenedioxymethamphetamine in Inducing Hyperactivity in Mice Lacking the Postsynaptic Scaffolding Protein SHANK1.

Genetic defects in the three SH3 and multiple ankyrin repeat domains (SHANK) genes (SHANK1, SHANK2, and SHANK3) are associated with multiple major neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BPD). Psychostimulant-induced hyperactivity is a commonly applied paradigm to assess behavioral phenotypes related to BPD and considered to be the gold standard for modeling mania-like elevated drive in mouse models. Therefore, the goal of our present study was to test whether Shank1 plays a role in the behavioral effects of psychostimulants and whether this is associated with genotype-dependent neurochemical alterations. To this aim, male and female null mutant Shank1-/- mice were treated with d-amphetamine (AMPH; 2.5 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, commonly known as ecstasy; 20 mg/kg), and psychostimulant-induced hyperactivity was compared to heterozygous Shank1+/- and wildtype Shank1+/+ littermate controls. Results show that Shank1-/- mice display reduced psychostimulant-induced hyperactivity, although psychostimulants robustly stimulated locomotor activity in littermate controls. Shank1 deletion effects emerged throughout development, were particularly prominent in adulthood, and seen in response to both psychostimulants, i.e., AMPH and MDMA. Specifically, while AMPH-induced hyperactivity was reduced but still detectable in Shank1-/- mice, MDMA-induced hyperactivity was robustly blocked and completely absent in Shank1-/- mice. Reduced efficacy of psychostimulants to stimulate hyperactivity in Shank1-/- mice might be associated with alterations in the neurochemical architecture in prefrontal cortex, nucleus accumbens, and hypothalamus. Our observation that psychostimulant-induced hyperactivity is reduced rather than enhanced in Shank1-/- mice clearly speaks against a behavioral phenotype with relevance to BPD. Lack of BPD-like phenotype is consistent with currently available human data linking mutations in SHANK2 and SHANK3 but not SHANK1 to BPD.

Value of Exhaled Nitric Oxide (FeNO) And Eosinophilia During the Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospital Admission.

The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3-6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm3) than the rest (CB: 23 ppb, 184 cells/mm3, emphysema: 27 ppb, 159 cells/mm3; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy.

Hepatic abscess as a complication of an abscessed gastric lipoma.

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Size constancy following long-term visual deprivation.

We can estimate the veridical size of nearby objects reasonably well irrespective of their viewing distance. This perceptual capability, termed size constancy, is accomplished by combining information about retinal image size together with the viewing distance, or using the relational information available in the scene, via direct perception [1]. A previous study [2] showed that children typically underestimate the size of a distant object. This underestimation is reduced with time, suggesting that years of visual experience may be essential for attaining true size constancy. But what if you have had very limited vision during the early years of life? We studied 23 Ethiopian children suffering from bilateral, early-onset cataract, who were surgically treated only years after birth. Surprisingly, most children were able to estimate object size reasonably well irrespective of distance; in fact, they usually tended to overestimate the far-object size. Closer examination indicated that, although before surgery the patients were diagnosed as having a full, mature bilateral cataract, they nevertheless had some residual form of vision, typically limited to very close range. Gandhi et al.[3] earlier reported immediate susceptibility to geometric visual illusions in a similar group of newly-sighted children, concluding that size constancy was probably innate. We suggest that their immediate ability to judge physical size irrespective of distance is more likely to result from their previous visual experience.

Is muscular atrophy a contraindication in laparoscopic abdominal wall defect repair? A prospective study.

Laparoscopic surgery for abdominal wall hernias improves short-term results as compared with open hernia surgery. However, no evidence exists to recommend this approach for pseudohernias, which are abdominal wall defects postsurgery caused by denervation and muscular atrophy. The purpose of this study is to analyze whether the laparoscopic approach benefits patients with a pseudohernia. A prospective nonrandomized, single-center clinical study was conducted of 24 patients operated on for pseudohernia. This study was designed with the basic principle of one unit, one surgeon, one mesh, and two techniques (laparoscopic or open double prosthetic repair). The primary end point was assessment of the abdominal wall according to: 1) abdominal perimeter; 2) computed tomography scan; and 3) degree of satisfaction. The secondary end points were intraoperative parameters and comorbidity. Laparoscopy offered no benefits in patients with pseudohernias. Open surgery offered no significant differences in intra- and postoperative morbidity, but if the initial weakness improved with a decrease in abdominal perimeter and visceral content, then there was more than 90 per cent satisfaction (P < 0.05). The laparoscopic approach does not improve the bulge caused by abdominal muscle atrophy. The option of a muscular and prosthetic reconstruction provides better clinical and cosmetic results.

[CT colonography vs. barium enema for the preoperative study of colorectal cancer in patients with incomplete colonoscopy]. / Colonografía tomográfica computarizada frente a enema opaco en el estudio preoperatorio del cáncer colorrectal en pacientes con colonoscopia incompleta.

BACKGROUND AND OBJECTIVE: The complete preoperative evaluation of the colon is necessary in colorectal cancer owing to the frequency of synchronous tumors. The objective of this paper was to evaluate the utility of the computed tomography colonography (CTC) as opposed to barium enema (BEDC) when the colonoscopy was incomplete or impossible to perform. PATIENTS AND METHOD: Group A: 50 patients with colorectal cancer with subsequent incomplete colonoscopy and BEDC. Group B: 40 patients with colorectal cancer with subsequent incomplete colonoscopy and CTC. As gold standard to match the tests, we carried out the pathological study of the surgical piece and the colonoscopy 3 months after surgery. In addition, we studied the degree of satisfaction, indirect effect and cost by test. RESULTS: There were no synchronous tumors. For the detection of colonic polyps, we obtained for the CTC the following values: Sensitivity = 85.7%, Specificity = 96.1%, PPV = 92.3%, NPV = 92.6%, CPP = 21,97 and CPN =0,15. And for BEDC, the values were: Sensitivity = 23.5%, Specificity = 92.8%, PPV = 80%, NPV = 71.7%, CPP = 3.26 and CPN = 0.82 (p < 0.001). The degree of satisfaction was greater with CTC than with BEDC (p < 0.05). There were no differences as far as indirect effect was concerned. The cost of CTC was 33.18 Euros and it was 42.42 Euros for BEDC. CONCLUSION: CTC is better than BEDC both to confirm the presence of polyps in colon and to rule out the absence of them in patients in whom a complete the study of the colon by colonoscopy has not been possible.

Colonografía tomográfica computarizada frente a enema opaco en el estudio preoperatorio del cáncer colorrectal en pacientes con colonoscopia incompleta / CT colonography vs barium enema for the preoperative study of colorectal cancer in patients with incomplete colonoscopy

Fundamento y objetivo: La evaluación preoperatoria completa del colon es necesaria, ya que el cáncer colorrectal se asocia con frecuencia a tumores sincrónicos. El objetivo de este trabajo es valorar la utilidad de la colonografía tomográfica computarizada (CTC) frente al enema opaco de doble contraste (EODC) cuando la colonoscopia fue incompleta o imposible de realizar. Pacientes y método: Grupo A: 50 pacientes con cáncer colorrectal, colonoscopia incompleta y EODC posterior. Grupo B: 40 pacientes con cáncer colorrectal, colonoscopia incompleta y CTC posterior. Como método de referencia para comparar los resultados obtenidos se utilizaron el estudio anatomopatológico de la pieza quirúrgica y la colonoscopia a los 3 meses de la cirugía. Además, se estudiaron el grado de satisfacción, los efectos secundarios y el coste por prueba. Resultados: No hubo tumores sincrónicos. Para la detección de pólipos colónicos obtuvimos para la CTC valores de sensibilidad (S) del 85,7%, especificidad (E) 96,1%, valor predictivo positivo (VPP) 92,3%, valor predictivo negativo (VPN) 92,6%, coeficiente de probabilidad positivo (CPP) 21,97 y coeficiente de probabilidad negativo (CPN) 0,15, y para el EODC valores de S del 23,5%, E del 92,8%, VPP del 80%, VPN del 71,7%, CPP del 3,26 y CPN del 0,82 (p < 0,001). El grado de satisfacción del paciente fue mayor con la CTC que con el EODC (p < 0,05). No hubo diferencias en cuanto a efectos secundarios. El coste de la CTC fue de 33,18 euros y el de la EODC, de 42,42 euros. Conclusión: La CTC es mejor que el EODC, tanto para confirmar la presencia de pólipos en el colon como para descartar la ausencia de éstos, en pacientes en los que no ha sido posible completar el estudio del colon por colonoscopia

Background and objective: The complete preoperative evaluation of the colon is necessary in colorectal cancer owing to the frequency of synchronous tumors. The objective of this paper was to evaluate the utility of the computed tomography colonography (CTC) as opposed to barium enema (BEDC) when the colonoscopy was incomplete or impossible to perform. Patients and method: Group A: 50 patients with colorectal cancer with subsequent incomplete colonoscopy and BEDC. Group B: 40 patients with colorectal cancer with subsequent incomplete colonoscopy and CTC. As gold standard to match the tests, we carried out the pathological study of the surgical piece and the colonoscopy 3 months after surgery. In addition, we studied the degree of satisfaction, indirect effect and cost by test. Results: There were no synchronous tumors. For the detection of colonic polyps, we obtained for the CTC the following values: Sensitivity = 85.7%, Specificity = 96.1%, PPV = 92.3%, NPV = 92.6%, CPP = 21,97 and CPN =0,15. And for BEDC, the values were: Sensitivity = 23.5%, Specificity = 92.8%, PPV = 80%, NPV = 71.7%, CPP = 3.26 and CPN = 0.82 (p < 0.001). The degree of satisfaction was greater with CTC than with BEDC (p < 0.05). There were no differences as far as indirect effect was concerned. The cost of CTC was 33.18 Euros and it was 42.42 Euros for BEDC. Conclusion: CTC is better than BEDC both to confirm the presence of polyps in colon and to rule out the absence of them in patients in whom a complete the study of the colon by colonoscopy has not been possible

VLAD. Un sistema gráfico de expresión continua de efectividad asistencial aplicado en medicina intensiva / The variable life adjusted display (VLAD). A graphical technique of continuous expression of healthcare effectiveness applied to intensive care medicine

Introducción: Se describen distintos métodos para estimar y expresar la efectividad en la asistencia a pacientes críticos. De entre ellos, se hace especial hincapié en el método VLAD (Variable Life Adjusted Display), que permite una descripción secuencial y continua, con expresión gráfica, fácilmente comprensible y utilizable. El objetivo del trabajo no es hacer una descripción de un nuevo método, sino la difusión de uno poco conocido y su aplicación a pacientes críticos. Material y método: Se describe la metodología de cálculo del método VLAD como resultado de la resta acumulada entre supervivientes reales y predichos supervivientes, por cualquiera de los métodos al uso utilizados para predecir mortalidad en pacientes críticos. Los autores utilizan el Simplified Acute Physiology Score 2. Resultados: El método se aplica a 7.448 pacientes, ingresados consecutivamente en una unidad de cuidados intensivos polivalente desde 1999 a 2004, incluido. Se ofrecen distintos gráficos según que la expresión VLAD se realice sobre la totalidad de la muestra, o sobre submuestras homogéneas (tipo de ingreso, o determinadas causas de ingreso). Discusión: Se ofrece una visión crítica de los medios de expresión de efectividad, desde una perspectiva de gestión clínica, y de sus potenciales aplicaciones: instrumento de gestión, revisión de la asistencia prestada, docencia e investigación

Introduction: Different methods for estimating and expressing effectiveness of the care of critically ill patients are described. Among them, especial interest is placed on VLAD methodology, which allows continuous and sequential expression of the variable under study through a graphic display that is easy to use and understand. The aim of this article was not to describe a new methodology, but rather to present a little-known method not previously used in critically-ill patients in Spain. Material and method: We describe the procedure for calculating VLAD as the result of the cumulative subtraction of real mortality from predicted mortality, irrespective of the methodology used for prediction. In the present article, SAPS 2 was used. Results: The method was applied in 7,448 patients consecutively admitted to a medical­surgical ICU from 1999 to 2004 (inclusive). Graphs depicting the use of VLAD in the whole sample and in homogeneous subgroups (type of admission or certain admission diagnoses) were obtained. Discussion: We provide a critical view of techniques for expressing effectiveness, from the perspective of clinical management, as well as of the possible uses of these techniques in healthcare management, quality evaluation, teaching, and research

Effect of isolation measures on the incidence and prevalence of hepatitis C virus infection in hemodialysis.

BACKGROUND: Nosocomial transmission of hepatitis C virus (HCV) in hemodialysis (HD) units is well established. In units with a high prevalence of HCV infection, the implementation of universal precautionary measures may not suffice in order to decrease the incidence and prevalence of HCV. In this setting strict isolation practices can be useful in order to achieve this goal. METHODS: The incidence and prevalence of HCV infection amongst all HD and peritoneal dialysis (PD) patients from the province of Albacete, Spain, have been studied from 1992 to 2003.Through the 1993-1995 period chronic HD patients were treated either in a room exclusively for HCV- patients or in a room shared by HCV+ and HCV- patients. Complete separation of HCV+ and HCV- patients was implemented in 1995. Acute patients have been separated since 1992. The implementation of universal precautions was applied throughout the period. RESULTS: There has not been a single seroconversion in the rooms where only HCV- patients were dialyzed during the 11 years of follow-up. There were two seroconversions in the rooms shared for 3 years by both HCV+ and HCV- patients. In 1995 the prevalence of HCV+ cases in HD and PD was 21.6 and 23.2%, respectively. Since then it has decreased steadily and in parallel for both therapies, and the current prevalence is 6.8% in HD and 5.7% in PD. CONCLUSIONS: In HD units with a high prevalence of HCV+ patients, strict isolation in combination with implementation of universal prevention measures can eliminate nosocomial transmission and obtain a long-term reduction in prevalence.

Desbridamiento de úlceras por presión y otras heridas crónicas / Debridement of pressure ulcers and other chronic wounds

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Treatment of tuberculosis with rifabutin in a renal transplant recipient.

Development of tuberculosis infection in a renal transplant patient is infrequent in Spain, although the prevalence is higher than in the general population. These patients usually receive calcineurin inhibitors as the main component of their immunosuppressive treatment. The metabolism of these drugs, whether cyclosporine or tacrolimus, involves cytochrome P-450 3A. Rifampin, a widely used agent in the treatment of tuberculosis, is also an important inducer of cytochrome P-450 3A metabolism and has the capacity to decrease serum levels of the calcineurin inhibitors. This metabolic interaction makes pharmacologic management of tuberculosis-infected transplant patients more complex and can result in a higher risk of acute rejection caused by decreased levels of the immunosuppressant in the blood. The authors present a case of a renal transplant patient with a soft tissue infection caused by Mycobacterium tuberculosis who was treated with rifabutin instead of rifampin, with excellent results in terms of graft survival and overall survival. The use of rifabutin allowed the authors to achieve better control of circulating immunosuppressant levels and a lower probability of acute graft rejection.

Perforación esofágica tras instrumentación con sonda de Sengstaken-Blakemore. A propósito de un caso / Esophageal perforation after Sengstaken-Blakemore probe use. Case study

La rotura del esófago es una complicación grave que se produce sobre todo después de la endoscopia realizada con fines terapéuticos, aunque se ha descrito asociada a cualquier tipo de instrumentación esofágica. Presentamos un caso de rotura de esófago después de intentar la hemostasia de una hemorragia digestiva alta, primero con escleroterapia y después por medio de una sonda de Sengstaken-Blakemore. Revisamos también los mecanismos que intervienen en las distintas formas de perforación iatrogénica. (AU)

Recomendaciones sobre la utilización de antisépticos en el cuidado de heridas crónicas / Guideliness on the antisepsis for chronic wounds care

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