Induced Heteroresistance in Carbapenem-Resistant Acinetobacter baumannii (CRAB) via Exposure to Human Pleural Fluid (HPF) and Its Impact on Cefiderocol Susceptibility.

Infections caused by Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates, such as hospital-acquired pneumonia (HAP), bacteremia, and skin and soft tissue infections, among others, are particularly challenging to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 and prescribed for the treatment of CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported a higher-than-average all-cause mortality rate in patients treated with cefiderocol compared to the best available therapy. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population that is seemingly isogenic. Recent results have demonstrated that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here, we describe the molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were resistant to cefiderocol. To identify mutations and gene expression changes associated with cefiderocol heteroresistance, we subjected these variants to whole genome sequencing and global transcriptional analysis. We then assessed the impact of these mutations on the pharmacodynamic activity of cefiderocol via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or ß-lactam resistance. However, transcriptional analyses demonstrated significant modifications in levels of expression of genes associated with iron-uptake systems or ß-lactam resistance. The blaNDM-1 and blaADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes' expression was reduced. One of the mutations common to both heteroresistant strains was mapped within ppiA, a gene associated with iron homeostasis in other species. Static time-kill assays demonstrated that supplementing cation-adjusted Mueller-Hinton broth with human serum albumin (HAS), the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. We conclude that exposing CRAB to fluids with high HSA concentrations facilitates the rise of heteroresistance associated with point mutations and transcriptional upregulation of genes coding for ß-lactamases and biofilm formation. The findings from this study hold significant implications for understanding the emergence of CRAB resistance mechanisms against cefiderocol treatment. This understanding is vital for the development of treatment guidelines that can effectively address the challenges posed by CRAB infections.

Cross-Sectional Analysis of Colombian University Students' Perceptions of Mental Health during the COVID-19 Pandemic: Repercussions on Academic Achievement.

BACKGROUND: During the COVID-19 pandemic, the increase in academic activities at home negatively impacted mental health, due to significant levels of stress, anxiety, and depression. We investigated the association of depression and anxiety with university students' academic performance during the COVID-19 lockdown in Bucaramanga, Colombia. MATERIALS AND METHODS: A cross-sectional study was conducted through an online survey during the lockdown, through the use of the Hospital Anxiety and Depression Scale (HADS) and the grade-point average. RESULTS: 1090 females, out of 1957 students, with mean age 22.2 ± 5.3 years, participated in the study. The prevalence of low academic performance was higher in men (4.7% p = 0.014). As for mental health, 2.5% of the students were classified as "definite cases" of anxiety and 8.2% were diagnosed with depression. Women with a low academic performance had a greater percentage of being "definite cases" (3.8%) of anxiety as compared to men (1.1%). Regarding depression, in men, 12.2% of those with low academic performance were "definite cases" (6.9% p < 0.05); in females with low academic performance, 10.1% were "definite cases" of depression, according to the Poisson regression analysis. The probability of low performance was 100% higher for women identified as "doubtful cases" of depression (PR = 2.0; 95% CI: 1.10-5.18, p = 0.03). CONCLUSIONS: A positive association between the severity of anxiety/depression and lower grades, especially in women, was found. Mental health should be a special concern when considering university students, in order to improve their academic performance.

Underwater cap-suction pseudopolyp formation for endoscopic mucosal resection: a simple technique for treating flat, appendiceal orifice or ileocecal valve colorectal lesions.

BACKGROUND: We aimed to evaluate the safety and technical success of an easy-to-use technique that applies underwater cap suction pseudopolyp formation to facilitate the resection of flat lesions or those at the appendiceal orifice or ileocecal valve. METHODS: We retrospectively analyzed a register of consecutive cap suction underwater endoscopic mucosal resection (CAP-UEMR) procedures performed at two centers between September 2020 and December 2021. Procedures were performed using a cone-shaped cap, extending 7 mm from the endoscope tip, to suction the lesion while submerged underwater, followed by underwater snare resection. Our primary end point was technical success, defined as macroscopic complete resection. RESULTS: We treated 83 lesions (median size 20 mm; interquartile range [IQR] 15-30 mm) with CAP-UEMR: 64 depressed or flat lesions (18 previously manipulated, 9 with difficult access), 11 from the appendix, and 8 from the ileocecal valve. Technical success was 100 %. There were seven intraprocedural bleedings and two delayed bleedings, all managed endoscopically. No perforations or other complications occurred. Among the 64 lesions with follow-up colonoscopy, only one recurrence was detected, which was treated endoscopically. CONCLUSIONS: CAP-UEMR was a safe and effective technique for removing nonpolypoid colorectal lesions, including those arising from the appendiceal orifice or ileocecal valve.

Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

BACKGROUND: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. METHODS/DESIGN: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. DISCUSSION: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04330846. Registered on 1 April 1 2020. https://clinicaltrials.gov/ct2/home.

Appropriateness of routine pre-endoscopic SARS-CoV-2 screening with RT-PCR in asymptomatic individuals and its impact on delayed diagnosis / Idoneidad del cribado pre-endoscópico rutinario de SARS-CoV-2 con RT-PCR en individuos asintomáticos y su impacto en la demora diagnóstica

Aims: Endoscopy units are considered to be at an increased risk of infection by SARS-CoV-2. Our aim is to assess the correlation between pre-endoscopic screening with reverse-transcription-polymerase-chain-reaction (RT-PCR) in asymptomatic individuals scheduled for elective endoscopy and the epidemiological data published by the local Health Administration. Patients and methods: Observational retrospective study collecting the results of our screening strategy spanning June/2020–June/2021, the effective potential growth (EPG), an index measuring the outbreak risk, and the 7 and 14-day cumulative incidence (CI). Indication, delay and the findings of the endoscopic examinations were registered for RT-PCR positive patients. Results: A total of 5808 tests were performed, yielding 125 positive results (2.15%). All positive tests occurred in weeks of high/very high risk (EPG>100) with the highest monthly rate being 9.36%, recorded in January/2021. A significant correlation (rho=0.796; p<0.001) between weekly positive rates and EPG was observed, and a significantly lower weekly number of positive tests was recorded when EPG<100. Planning the screening strategy one week ahead according to EPG>100 would have avoided up to 826 tests with only one positive result to account for. One hundred and thirteen individuals tested positive and 89 endoscopies were delayed. The most common findings were colon polyps, colorectal cancer and gastric metaplasia. Oncological diagnosis was delayed 50±3 days. Conclusions: No positive RT-PCR test were registered out of high-risk periods. Epidemiological administrative data in the preceding two weeks showed a significant correlation with screening results and could be useful to plan pre-endoscopic screening and avoid unnecessary tests.(AU)

Antecedentes: La actividad endoscópica comporta un riesgo elevado de transmisión de la infección por SARS-CoV-2. Nuestro objetivo es valorar la correlación entre el cribado pre-endoscópico con reverse-transcription-polymerase-chain-reaction (RT-PCR) en individuos asintomáticos programados para una endoscopia ambulatoria y los datos epidemiológicos publicados por el departamento de salud pública. Pacientes y métodos: Estudio observacional retrospectivo de los resultados del cribado realizado entre junio/2020 y junio/2021. Se registró el índice de crecimiento potencial (ICP) y la incidencia acumulada a 7 y 14 días. En los pacientes con RT-PCR positiva se registraron indicación, demora y hallazgos endoscópicos. Resultados: Se identificaron un total de 5.808 test con 125 resultados positivos (2,15%). Todos los resultados positivos se registraron en semanas consideradas de alto/muy alto riesgo (ICP>100), con una tasa máxima de positivos del 9,26% en enero/2021. Se observó una correlación significativa (rho=0,796; p<0,001) entre la tasa de positivos y el ICP, así como una diferencia estadísticamente significativa con la tasa de positivos en las semanas con el ICP<100. Planificar el cribado acorde al ICP>100 en la semana previa, habría evitado hasta 876 test, con un único resultado positivo. Ciento trece pacientes resultaron positivos y se demoraron 89 endoscopias; los hallazgos más frecuentes fueron pólipos, cáncer colorrectal y metaplasia gástrica. El diagnóstico oncológico se demoró 50±3 días. Conclusiones: No se registraron RT-PCR positivas fuera de los períodos de alto riesgo. Los datos epidemiológicos de las dos semanas anteriores mostraron una correlación significativa con los resultados del cribado y podrían ser útiles para planificar el mismo y evitar pruebas innecesarias.(AU)

Benefit of extending the protocol for high resolution manometry according to the version 4.0 of the Chicago criteria. A multicenter study.

BACKGROUND: The last version of the Chicago Criteria for high resolution esophageal manometry proposes an expanded protocol including complementary maneuvers to improve the diagnostic yield of the exploration. Our aim was to determine the diagnostic gain of the CCv4.0 protocol compared to the CCv3.0 protocol. METHODS: All manometry recordings performed in 4 reference centers during the first 10 months after the implementation of the new protocol were retrospectively reviewed. The time spent to complete the protocol was measured, and the changes in diagnosis resulting from the new CCv4.0 were compared to CCv3.0. KEY RESULTS: From a total of 756 HRM performed, 606 studies could be properly analyzed. The duration of the studies was 18.3 ± 4.3 min. From these, 11.3 ± 3.4 min were spent to complete the CCv3.0 protocol, and 7.4 ± 3.6 min were spent for the remaining maneuvers. A discordant diagnosis between CCv3.0 and CCv4.0 was obtained in 12% of patients: 32% of patients with ineffective esophageal motility turned to normal motility; 24% of patients with esophagogastric junction outlet obstruction (EGJOO) turned to a non-obstructive disorder; and 1% of patients with an apparently normal EGJ relaxation, turned to an obstructive disorder. EGJOO according to CCv4.0 was more prevalent in patients referred for dysphagia (11%) than those referred for GERD (4%; p = 0.003). CONCLUSIONS AND INFERENCES: Prolongation of the time spent to complete the CCv4.0 protocol leads to a change in the diagnosis of 12% of patients. Clinically relevant changes are mainly related to the evaluation of EGJOO.

Appropriateness of routine pre-endoscopic SARS-CoV-2 screening with RT-PCR in asymptomatic individuals and its impact on delayed diagnosis.

AIMS: Endoscopy units are considered to be at an increased risk of infection by SARS-CoV-2. Our aim is to assess the correlation between pre-endoscopic screening with reverse-transcription-polymerase-chain-reaction (RT-PCR) in asymptomatic individuals scheduled for elective endoscopy and the epidemiological data published by the local Health Administration. PATIENTS AND METHODS: Observational retrospective study collecting the results of our screening strategy spanning June/2020-June/2021, the effective potential growth (EPG), an index measuring the outbreak risk, and the 7 and 14-day cumulative incidence (CI). Indication, delay and the findings of the endoscopic examinations were registered for RT-PCR positive patients. RESULTS: A total of 5808 tests were performed, yielding 125 positive results (2.15%). All positive tests occurred in weeks of high/very high risk (EPG>100) with the highest monthly rate being 9.36%, recorded in January/2021. A significant correlation (rho=0.796; p<0.001) between weekly positive rates and EPG was observed, and a significantly lower weekly number of positive tests was recorded when EPG<100. Planning the screening strategy one week ahead according to EPG>100 would have avoided up to 826 tests with only one positive result to account for. One hundred and thirteen individuals tested positive and 89 endoscopies were delayed. The most common findings were colon polyps, colorectal cancer and gastric metaplasia. Oncological diagnosis was delayed 50±3 days. CONCLUSIONS: No positive RT-PCR test were registered out of high-risk periods. Epidemiological administrative data in the preceding two weeks showed a significant correlation with screening results and could be useful to plan pre-endoscopic screening and avoid unnecessary tests.

Effect of intracolonic volume on gastric sensory-motor responses in constipation-predominant irritable bowel syndrome.

BACKGROUND: Interaction between gut stimuli may induce symptom overlap in patients with functional gastrointestinal disorders. The aim is to determine the effect of increased volumes of colonic contents on gastric sensory/motor responses and satiety in patients with constipation-predominant irritable bowel syndrome (IBS-C) and overlapping dyspeptic symptoms, and a cohort of healthy subjects. METHODS: In 15 patients with IBS-C and 10 healthy subjects, the effect of real versus sham colonic filling with gas (1080 ml) on gastric sensitivity (measured by stepwise distensions of the stomach), gastric compliance, abdominal perception, and nutrient drink tolerance was studied on separate days. RESULTS: In healthy subjects, colonic gas filling induced an increment in gastric sensitivity to distension (mean score 2.0 ± 0.2 before, and 3.0 ± 0.4 after; p = 0.038). In IBS, basal sensitivity was greater and remained unchanged after colonic gas filling (score 4.0 ± 0.1 and 3.8 ± 0.3, respectively; p < 0.001 vs. basal in health). Colonic gas infusion induced abdominal symptoms that were significantly greater in IBS-C (score 2.6 ± 0.1) than in health (score 1.7 ± 0.4; p = 0.027), with minor changes in gastric tone, and no changes in gastric compliance in both groups. Colonic filling produced a profound reduction in nutrient drink tolerance in IBS (791 ± 87 ml sham filling, 491 ± 58 ml gas filling; p < 0.001) but only a minor reduction in health (940 ± 70 ml sham filling, 860 ± 94 ml gas filling; p = 0.223). CONCLUSIONS & INFERENCES: The volume of the colonic contents modulates satiety in patients with IBS-C, due to a general visceral pan-hypersensitivity. These effects should be considered in the choice of treatment for constipation in these patients.

Central de Resultados del ámbito sociosanitario en Cataluña. Evolución 2013-2018 / Results Centre of Social and Health Care Network in Catalonia. Evolution 2013–2018

Objetivo : La Central de Resultados (CdR) nace con la misión de medir, evaluar y difundir los resultados alcanzados por los diferentes agentes del sistema sanitario, en base a medidas relevantes. El objetivo de este trabajo es describir la evolución de los indicadores utilizados en la CdR del ámbito sociosanitario (CdR-SS), incluyendo algunos indicadores sensibles a la práctica enfermera.Método: Estudio observacional, descriptivo y transversal de los 6 informes de CdR-SS (2013-2018). Se analizan indicadores que incluyen actividad realizada, días de estancia, consecución de objetivos rehabilitadores, altas a domicilio, mortalidad y úlceras por presión.Resultados: Hubo un aumento de la actividad en las diferentes líneas y una disminución en los días de estancia. Los resultados mostraron heterogeneidad entre centros. La mejora funcional y las altas a domicilio mostraron una tendencia creciente, mientras que la mortalidad tendió a disminuir. Se mantuvo estabilidad en la prevalencia de úlceras por presión de grados iii-iv.Conclusiones: La CdR-SS ha incluido diferentes indicadores en los diversos informes para mejorar la capacidad de evaluación y benchmarking sociosanitario. Los informes de CdR-SS aportan transparencia y rendimiento de cuentas del ámbito e invitan a profundizar en la mejora de este sector, mostrando que evoluciona hacia la atención intermedia con la entrada de subagudos y la mayor eficiencia de convalecencia. La incorporación de indicadores sensibles a la práctica enfermera contribuye a visibilizar los cuidados y al colectivo enfermero. (AU)

Objective: The Results Centre's (RC) mission is to measure, evaluate and disseminate the results achieved by the different agents of the health system, based on relevant measures. The purpose of this research is to describe the evolution of indicators used in the social and health care network RC (RC-SH), including some indicators sensitive to nursing practice.Method: Observational, descriptive cross-sectional study based on data from 6 RC-SH reports (2013–2018). Indicators including activity carried out, days of stay, achievement of rehabilitation goals, discharge to home, mortality and pressure ulcers are analysed.Results: There was an increase in activity on the different social and health resources and days of stay decrease. Results were heterogeneous between centres. Functional improvement and home discharge showed an increasing trend, while mortality tended to decrease. The prevalence of grade III–IV pressure ulcers was maintained.Conclusions: RC-SH reports have included different indicators to improve the capacity of evaluation and benchmarking for social and health network. These reports provide transparency and accountability in the field and invite further improvement in this sector. Also RC-SH results show that social and health network evolves towards intermediate care with the entry of subacute resources and the greater efficiency of convalescence. The incorporation of indicators sensitive to nursing practice contributes to making nurses and nursing care visible. (AU)

[Results Centre of Social and Health Care Network in Catalonia. Evolution 2013-2018]. / Central de Resultados del ámbito sociosanitario en Cataluña. Evolución 2013-2018.

OBJECTIVE: The Results Centre's (RC) mission is to measure, evaluate and disseminate the results achieved by the different agents of the health system, based on relevant measures. The purpose of this research is to describe the evolution of indicators used in the social and health care network RC (RC-SH), including some indicators sensitive to nursing practice. METHOD: Observational, descriptive cross-sectional study based on data from 6 RC-SH reports (2013-2018). Indicators including activity carried out, days of stay, achievement of rehabilitation goals, discharge to home, mortality and pressure ulcers are analysed. RESULTS: There was an increase in activity on the different social and health resources and days of stay decrease. Results were heterogeneous between centres. Functional improvement and home discharge showed an increasing trend, while mortality tended to decrease. The prevalence of grade III-IV pressure ulcers was maintained. CONCLUSIONS: RC-SH reports have included different indicators to improve the capacity of evaluation and benchmarking for social and health network. These reports provide transparency and accountability in the field and invite further improvement in this sector. Also RC-SH results show that social and health network evolves towards intermediate care with the entry of subacute resources and the greater efficiency of convalescence. The incorporation of indicators sensitive to nursing practice contributes to making nurses and nursing care visible.

The Brief Esophageal Dysphagia Questionnaire shows better discriminative capacity for clinical and manometric findings than the Eckardt score: Results from a multicenter study.

INTRODUCTION: Grading dysphagia is crucial for clinical management of patients. The Eckardt score (ES) is the most commonly used for this purpose. We aimed to compare the ES with the recently developed Brief Esophageal Dysphagia Questionnaire (BEDQ) in terms of their correlation and discriminative capacity for clinical and manometric findings and evaluate the effect of gastroesophageal reflux symptoms on both. METHODS: Symptomatic patients referred for high-resolution manometry (HRM) were prospectively recruited from seven centers in Spain and Latin America. Clinical data and several scores (ES, BEDQ, GERDQ) were collected and contrasted to HRM findings. Standard statistical analysis was performed. KEY RESULTS: 426 patients were recruited, 31.2% and 41.5% being referred exclusively for dysphagia and GERD symptoms, respectively. Both BEDQ and ES were independently associated with achalasia. Only BEDQ was independently associated with being referred for dysphagia and with relevant HRM findings. ROC curve analysis for achalasia diagnosis showed AUC of 0.809 for BEDQ and 0.765 for ES, with the main difference being higher BEDQ sensitivity (80.0% vs 70.8% for ES). GERDQ independently predicted ES but not BEDQ. In the absence of dysphagia (BEDQ = 0), GERD symptoms significantly determine ES. CONCLUSIONS AND INFERENCES: Our study suggests both the BEDQ and ES can complementarily describe symptomatic burden in achalasia. BEDQ has several advantages over the ES in the dysphagia evaluation, basically due to its higher sensitivity for manometric diagnosis and independence of GERD symptoms. ES should be used as an achalasia-specific metric, while BEDQ is a better symptom-generic evaluating tool.

Breaks in peristaltic integrity predict abnormal esophageal bolus clearance better than contraction vigor or residual pressure at the esophagogastric junction.

BACKGROUND: High-resolution impedance manometry (HRIM) evaluates esophageal peristalsis and bolus transit. We used esophageal impedance integral (EII), the ratio between bolus presence before and after an expected peristaltic wave, to evaluate predictors of bolus transit. METHODS: From HRIM studies performed on 61 healthy volunteers (median age 27 years, 48%F), standard metrics were extracted from each of 10 supine water swallows: distal contractile integral (DCI, mmHg cm s), integrated relaxation pressure (IRP, mmHg), and breaks in peristaltic integrity (cm, using 20 mmHg isobaric contour). Pressure and impedance coordinates for each swallow were exported into a dedicated, python-based program for EII calculation (EII ratio ≥ 0.3 = abnormal bolus clearance). Univariate and multivariate analyses were performed to assess predictors of abnormal bolus clearance. KEY RESULTS: Of 591 swallows, 80.9% were intact, 10.5% were weak, and 8.6% failed. Visual analysis overestimated abnormal bolus clearance compared to EII ratio (p ≤ 0.01). Bolus clearance was complete (median EII ratio 0.0, IQR 0-0.12) in 82.0% of intact swallows in contrast to 53.3% of weak swallows (EII ratio 0.29, IQR 0.0-0.57), and 19.6% of failed swallows (EII ratio 0.5, IQR 0.34-0.73, p < 0.001). EII correlated best with break length (ρ = 0.52, p < 0.001), compared to IRP (ρ: -0.17) or DCI (ρ: -0.42). On ROC analysis, breaks predicted abnormal bolus transit better than DCI or IRP (AUC 0.79 vs. 0.25 vs. 0.44, p ≤ 0.03 for each). On logistic regression, breaks remained independently predictive of abnormal bolus transit (p < 0.001). CONCLUSIONS & INFERENCES: Breaks in peristaltic integrity predict abnormal bolus clearance better than DCI or IRP in healthy asymptomatic subjects.