Long-Term Neuropsychiatric, Neurocognitive, and Functional Outcomes of Patients Receiving ECMO: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES: Despite the common occurrence of neurologic complications during extracorporeal membrane oxygenation (ECMO) support, data on long-term neuropsychiatric, neurocognitive, and functional outcomes are sparse. We aimed to determine the prevalence of long-term neuropsychiatric symptoms, neurocognitive and functional impairment, and favorable neurologic outcomes in adult patients who receive ECMO. METHODS: PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for text related to ECMO and neuropsychiatric, neurocognitive, and functional outcomes from inception to May 3, 2023. Our primary outcome was the prevalence of neuropsychiatric symptoms (pain/discomfort, anxiety, depression, posttraumatic stress disorder [PTSD], and sleep disturbance) at long-term (≥6 months) follow-up. Our secondary outcomes were the prevalence of neurocognitive impairment (memory, attention, and reasoning), functional impairment (daily activities, physical activity/mobility, and personal/self-care), and favorable neurologic outcomes (Cerebral Performance Category ≤2, modified Rankin scale ≤3, or Glasgow Outcome Scale ≥4). This study was registered in PROSPERO (CRD42023420565). RESULTS: We included 59 studies with 3,280 patients (median age 54 years, 69% male). The cohort consisted of 86% venoarterial (VA)-ECMO (n = 2,819) and 14% venovenous (VV)-ECMO (n = 461) patients. More than 10 tools were used to assess neuropsychiatric and neurocognitive outcomes, indicating a lack of standardization in assessment methodologies. The overall prevalence of neuropsychiatric symptoms was 41% (95% CI 33%-49%): pain/discomfort (52%, 95% CI 42%-63%), sleep disturbance (37%, 95% CI 0%-98%), anxiety (36%, 95% CI 27%-46%), depression (31%, 95% CI 22%-40%), and PTSD (18%, 95% CI 9%-29%). The prevalence of neurocognitive impairment was 38% (95% CI 13%-65%). The prevalence of functional impairment was 52% (95% CI 40%-64%): daily activities (54%, 95% CI 41%-66%), mobility (41%, 95% CI 28%-54%), and self-care (21%, 95% CI 13%-31%). The prevalence of neuropsychiatric symptoms in VV-ECMO patients was higher than that in VA-ECMO patients (55% [95% CI 34%-75%] vs 32% [95% CI 23%-41%], p = 0.01), though the prevalence of neurocognitive and functional impairment was not different between the groups. The prevalence of favorable neurologic outcomes was not different at various follow-ups: 3 months (23%, 95% CI 12%-36%), 6 months (25%, 95% CI 16%-35%), and ≥1 year (28%, 95% CI 21%-36%, p = 0.68). DISCUSSION: A substantial proportion of ECMO patients seemed to experience neuropsychiatric symptoms and neurocognitive and functional impairments at long-term follow-up. Considerable heterogeneity in methodology for gauging these outcomes exists, warranting the need for standardization. Multicenter prospective observational studies are indicated to further investigate risk factors for these outcomes in ECMO-supported patients.

WssI from the Gram-negative bacterial cellulose synthase is an O-acetyltransferase that acts on cello-oligomers with several acetyl donor substrates.

In microbial biofilms, bacterial cells are encased in a self-produced matrix of polymers (e.g., exopolysaccharides) that enable surface adherence and protect against environmental stressors. For example, the wrinkly spreader phenotype of Pseudomonas fluorescens colonizes food/water sources and human tissue to form robust biofilms that can spread across surfaces. This biofilm largely consists of bacterial cellulose produced by the cellulose synthase proteins encoded by the wss (WS structural) operon, which also occurs in other species, including pathogenic Achromobacter species. Although phenotypic mutant analysis of the wssFGHI genes has previously shown that they are responsible for acetylation of bacterial cellulose, their specific roles remain unknown and distinct from the recently identified cellulose phosphoethanolamine modification found in other species. Here, we have purified the C-terminal soluble form of WssI from P. fluorescens and Achromobacter insuavis and demonstrated acetylesterase activity with chromogenic substrates. The kinetic parameters (kcat/KM values of 13 and 8.0 M-1 s-1, respectively) indicate that these enzymes are up to four times more catalytically efficient than the closest characterized homolog, AlgJ from the alginate synthase. Unlike AlgJ and its cognate alginate polymer, WssI also demonstrated acetyltransferase activity onto cellulose oligomers (e.g., cellotetraose to cellohexaose) with multiple acetyl donor substrates (p-nitrophenyl acetate, 4-methylumbelliferyl acetate, and acetyl-CoA). Finally, a high-throughput screen identified three low micromolar WssI inhibitors that may be useful for chemically interrogating cellulose acetylation and biofilm formation.

Patient Safety Indicator 04 Does Not Consistently Identify Failure to Rescue in the Neurosurgical Population.

BACKGROUND: Improving neurosurgical quality metrics necessitates the analysis of patient safety indicator (PSI) 04, a measure of failure to rescue (FTR). OBJECTIVE: To demonstrate that PSI 04 is not an appropriate measure for capturing FTR within neurosurgery. METHODS: We conducted a single-center retrospective cohort study. Patients from January 1, 2017 to June 1, 2021, who sustained a PSI 04-attributed complication (pneumonia, deep vein thrombosis/pulmonary embolism, sepsis, shock/cardiac arrest, or gastrointestinal hemorrhage/acute ulcer), underwent a neurosurgical procedure, had inpatient mortality, and were identified using patient safety indicator 04 (PSI 04) tracking algorithm. The primary outcome was whether the attributed PSI 04 designation was the primary driver of mortality. RESULTS: We identified 67 patients who met the PSI 04 criteria (median age, 61 years; female sex, 43.4%). Nearly 20% of patients met the PSI complication criteria before admission. Patients who underwent emergent bedside procedures were more likely to present with a poor Glasgow Coma Scale ( P = .016), more likely to be intubated before admission ( P = .016), and less likely to have mortality due to a PSI 04-related complication ( P = .002). PSI 04-related complications were identified as the cause of death in only 43.2% of cases. Procedures occurring in the interventional radiology suite (odds ratio, 23.2; 95% CI, 3.5-229.3; P = .003) or the operating room (odds ratio, 6.2; 95% CI, 1.25-39.5; P = .03) were more likely to have mortality because of a PSI 04-related complication compared with bedside procedures. CONCLUSION: In total, 65.7% of patients were inappropriately flagged as meeting PSI 04 criteria. PSI 04 currently identifies patients with complications unrelated to operating room procedures. Improvement in patient safety within neurosurgery necessitates the development of a subspecialty specific measure to capture FTR.

Cardiovascular risk in hashimoto thyroiditis patients according to their thyroid state: a cross-sectional study / Riesgo cardiovascular en pacientes con tiroiditis hashimoto según su estada tiroidea: un estudio transversal

Objetivo: investigar la asociación entre los factores de riesgo cardiovascular y el nivel de riesgo cardiovascular con el estado tiroideo de pacientes con Tiroiditis de Hashimoto. Métodos y técnicas: treinta y ocho adultos con tiroiditis de Hashimoto participaron en este estudio descriptivo transversal. Los factores de riesgo cardiovascular considerados incluyeron edad, sexo, presión arterial, índice de masa corporal, glucemia, perfil lipídico, comorbilidades cardiovasculares, Proteína C Reactiva y Eritrosedimentación. Se utilizó la calculadora de riesgo cardiovascular de Framingham. La muestra se clasificó según el estado tiroideo en eutiroidismo (n = 15), hipotiroidismo clínico (n = 9) e hipotiroidismo subclínico (n = 13) e incluyó la presencia de anticuerpos antitiroideos. Se utilizó la prueba exacta de Fisher para determinar la asociación entre las variables estudiadas. Resultados: el 100 % de la muestra fue de sexo femenino; con una edad media entre 39-59 años. La categoría con bajo riesgo fue la mayor muestra (n = 30), equivalente al 78,9 %; riesgo moderado, no se obtuvo ningún paciente; alto riesgo (n = 8) constituyó el 21,1 %. Se encontró significancia estadística entre la edad y el nivel de riesgo cardiovascular en pacientes con hipotiroidismo clínico (p < 1), score in patients with clinical hypothyroidism was found (p < 1), IC 95 %. El nivel de glucosa en el hipotiroidismo subclínico y el hipotiroidismo clínico tuvo significancia estadística. Del mismo modo, se demostró que la presencia de antitiroglobulina (antiTg) está estrechamente relacionada con el nivel de riesgo cardiovascular en pacientes con hipotiroidismo subclínico. Conclusión: la edad, la glucemia, los anti-Tg, el antecedente de diabetes mellitus, la dislipemia y haber padecido algún accidente cerebrovascular se ha relacionado con un aumento del riesgo de desarrollar un evento cardiovascular hasta en 10 años en función de su perfil tiroideo. No se encontró evidencia de una relación directa entre la puntuación de riesgo cardiovascular y el estado de la tiroides en los participantes de este estudio.

Aims: To investigate the association between cardiovascular risk factors and cardiovascular risk score with the thyroid status of patients with Hashimoto's Thyroiditis. Methods: Thirty-eight consenting adults with Hashimoto's Thyroiditis participated in this cross-sectional study. The cardiovascular risk factors considered included age, sex, blood pressure, body mass index, fast blood glucose, lipid profile, cardiovascular comorbidities, C reactive protein, and erythrocyte sedimentation rate. The Framingham CV risk score was performed. The sample was classified into euthyroid (n = 15), clinical hypothyroidism (n = 9), and subclinical hypothyroidism (n = 13), and included the presence of antithyroid antibodies. Fisher's exact test was used to determine the association between the variables studied. Results: 100% of the sample were women; a mean age between 39-59 years old. The category with low risk was the largest (n = 30), equivalent to 78.9%; moderate risk, no patient was obtained; high risk (n = 8) constituted 21.1%. Statistical significance between age and CV risk score in patients with clinical hypothyroidism was found (p < 1), 95% CI. The glucose level in the subclinical hypothyroidism and clinical hypothyroidism had statistical significance. The presence of anti-Thyroglobulin (antiTg) was shown to be closely related to the level of CV risk in patients with subclinical hypothyroidism. Conclusion: Age, glycemia, anti-Tg, history of DM, dyslipidemia, or cerebrovascular accidents have been linked to raising the risk of developing CVD in up to 10 years depending on their thyroid profile. No evidence of a direct relationship between CV risk score and thyroid state was found in the participants of this study.

Facilitating Timely Institutional Review Board Review: Common Issues and Recommendations.

Review of clinical research by institutional review boards (IRBs) is integral to the protection of human subjects and necessary for the conduct of legal and ethical research. Because such review is time and resource intensive, it is critical to identify common issues that contribute to delayed review and approval of research. Hence, the aim of this quality improvement project was to identify factors associated with long delays in IRB approval and identify potential strategies to streamline the review process. In collaboration with the human subjects research protection program at a large academic health center in the northeastern United States, we conducted a content analysis of minutes of convened IRB meetings for every new protocol (initial submission) approved between January and September 2019 that required greater than or equal to two full board reviews prior to approval (n = 33). We also examined characteristics of new protocols that were reviewed less than twice at convened meetings during the same time frame (n = 244). Using χ2 or Fisher's exact tests, the characteristics of protocols with multiple reviews by the convened IRBs were compared with those protocol submissions reviewed by the convened IRBs only once. Three factors significantly associated with increased delays were researcher conflict of interest (30% vs. 12%, respectively, p < .01), need for radiation safety evaluation (36% vs. 20%, respectively, p = .03), and protocols that were clinical trials (73% vs. 60%, respectively, p < .01). Other factors associated with delayed IRB approval were excessive technical jargon (93.94%, n = 31), inadequate description of data security or inability to meet data security requirements of the institution (75.76%, n = 25), protocol design affecting patient safety (57.58%, n = 19), and lack of clarity regarding compensation and payment or study duration (n = 18, 54.54% each). Approaches to mitigate delays in approval and increase the efficiency and efficacy of the IRB process are recommended.

Grating Visual Acuity in phakic, aphakic, and pseudophakic Poodles.

OBJECTIVE: To compare the grating visual acuity (VA) measured by visual evoked potentials (VEP) in phakic, aphakic, and pseudophakic Poodles. ANIMALS STUDIED: Thirty-six Poodle dogs aged from 4 to 14 years. PROCEDURES: Animals were allocated into three different groups according to their lens status: phakic group (n = 12), aphakic group (n = 12), and pseudophakic group (n = 12). Grating VA was measured in cycles/degree (cpd) in all animals using the electrodiagnosis system Roland RETIport® in a dark room without using any mydriatic, sedative, or anesthetic drugs. RESULTS: The mean grating VA in the phakic, aphakic, and pseudophakic groups was 5.9 ± 1.0 cpd (20/102-Snellen equivalent), 2.6 ± 0.7 cpd (20/231), and 5.2 ± 1.1 cpd (20/116), respectively. The VA from aphakic eyes was significantly lower when compared to the phakic and pseudophakic eyes (P < .05). There was no significant difference in VA between phakic and pseudophakic eyes. CONCLUSIONS: The VEP is a useful tool for the evaluation of grating visual acuity in canines. The study showed that IOL implantation following phacoemulsification results in improved VA as measured by VEP compared to that of the aphakic eye and resulted in VA that was similar to that of the normal eye.

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site.

Mycobacterium tuberculosis is the cause of the world's most deadly infectious disease. Efforts are underway to target the methionine biosynthesis pathway, as it is not part of the host metabolism. The homoserine transacetylase MetX converts L-homoserine to O-acetyl-L-homoserine at the committed step of this pathway. In order to facilitate structure-based drug design, we determined the high-resolution crystal structures of three MetX proteins, including M. tuberculosis (MtMetX), Mycolicibacterium abscessus (MaMetX), and Mycolicibacterium hassiacum (MhMetX). A comparison of homoserine transacetylases from other bacterial and fungal species reveals a high degree of structural conservation amongst the enzymes. Utilizing homologous structures with bound cofactors, we analyzed the potential ligandability of MetX. The deep active-site tunnel surrounding the catalytic serine yielded many consensus clusters during mapping, suggesting that MtMetX is highly druggable.

Prevalence of Concurrent Prescribing of ACE-Is and ARBs among Beneficiaries of Puerto Rico's Government-Sponsored Health Care Plan During 2012 and 2013.

OBJECTIVE: Cardiovascular conditions are the second cause of death in Puerto Rico. The individual use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) is considered the first-line therapy for the treatment of several cardiovascular-related medical conditions. However, the concurrent use of these 2 therapeutic classes of drugs is not supported by treatment guidelines. Studies have shown that their concurrent use represents a potential health risk. The research described in this paper aimed to determine the prevalence of the concurrent prescription of ACE-Is and ARBs, either separately or as a combination product, in a group of beneficiaries of the Puerto Rico Health Services Administration (ASES, by its initials in Spanish). METHODS: A 2-year cross sectional study was conducted. All pharmacy claims from the years 2012 and 2013 were provided by ASES and subsequently evaluated by the investigators to identify those involving the prescription of an ACE-I, an ARB, or a combination of drugs belonging to both therapeutic classes. Each pharmacy claim was complemented with sociodemographic and clinical data. The final dataset was analyzed at the person-month level using frequency, cumulative frequency, percentage, and cumulative percentage. RESULTS: The final sample consisted of 361,841 beneficiaries. A total of 23,598 beneficiaries were excluded because of incomplete diagnostic information. Of the beneficiaries with complete information, 36,202 out of 338,243 (10.7%) had concurrent prescriptions for ACE-Is and ARBs during the study period. We excluded 1,124 beneficiaries who had a primary diagnosis of HF, resulting in a final pool of 35,078 beneficiaries (10.4%) who had prescriptions for combination products. CONCLUSION: An unacceptable pattern of ACE-I and ARB co-prescribing during the years 2012 and 2013 was observed in patients with diagnoses for which the combination is not clinically indicated.

Syntactic class influences phonological priming of tip-of-the-tongue resolution.

During tip-of-the-tongue (TOT) experiences, phonologically related words have both facilitated and impeded word retrieval. In the present experiment, we examined whether phonologically related words' syntactic class (part of speech) is responsible for these differential effects. Sixty college students saw general knowledge questions whose answers were designated target words and responded "know," "don't know," or "TOT." Following "TOT" and "don't know" responses, the participants saw five words, one of which was a prime. The primes contained the target's first syllable and either shared or did not share the target's part of speech. Following presentation of the primes, retrieval of the target was attempted again. Different-part-of-speech primes facilitated resolution of TOT states, whereas same-part-of-speech primes had no effect, relative to phonologically unrelated words. These results support node structure theory's most-primed-wins principle and the transmission deficit model account of TOT states and detail the importance of syntactic class in the selection of words that are candidates for speech production.