Effect of a national guideline on postoperative troponin surveillance: a retrospective cohort study.

PURPOSE: We aimed to evaluate the effect of the 2017 Canadian Cardiovascular Society (CCS) guidelines on troponin surveillance after noncardiac surgery. METHODS: This was a single-centre, retrospective, observational study. Patients aged 40 yr or older undergoing intermediate- to high-risk elective noncardiac surgery between 2016 and 2021 were included. We compared the number and percentage of troponin tests ordered before and after the guidelines were published and compared patient characteristics, specifically cardiovascular comorbidity, using odds ratio's (OR) with 95% confidence intervals (CIs). Outcomes were myocardial injury, myocardial infarction (MI), and in-hospital mortality. RESULTS: The cohort included 36,386 patients and the median age was 63 yr. Between 2016 and 2018, troponin surveillance was done in 2,461 (13%) of the 19,046 patients, compared with 2,398 (14%) of the 17,340 patients who had surgery between 2019 and 2021 (OR, 1.08; 95% CI, 1.02 to 1.15). Patients who had surgery in the second period had less cardiovascular comorbidity; the adjusted OR for troponin surveillance was 1.14 (95% CI, 1.07 to 1.21). In the two periods, troponin was elevated in 561 (2.9%) and 470 (2.7%) patients, an MI was documented in 54 (0.3%) and 36 (0.2%) patients, and 95 (0.5%) and 73 (0.4%) patients died, respectively. After adjustment for baseline differences in the two periods, the ORs for MI and mortality were 0.83 (95% CI, 0.54 to 1.27) and 0.88 (95% CI, 0.64 to 1.19), respectively. CONCLUSION: Although the odds of troponin ordering were slightly but significantly higher after publication of the CCS guidelines, the odds for detecting an MI and for mortality did not change.

RéSUMé: OBJECTIF: Notre objectif était d'évaluer l'effet des lignes directrices 2017 de la Société canadienne de cardiologie (SCC) sur le monitorage de la troponine après une chirurgie non cardiaque. MéTHODE: Il s'agissait d'une étude observationnelle rétrospective monocentrique. Les patient·es âgé·es de 40 ans ou plus bénéficiant d'une chirurgie non cardiaque non urgente à risque intermédiaire à élevé entre 2016 et 2021 ont été inclus·es. Nous avons comparé le nombre et le pourcentage de tests de troponine prescrits avant et après la publication des lignes directrices et comparé les caractéristiques des patient·es, en particulier la comorbidité cardiovasculaire, en utilisant le rapport de cotes (RC) avec des intervalles de confiance (IC) à 95 %. Les critères d'évaluation comprenaient les lésions myocardiques, l'infarctus du myocarde (IM) et la mortalité hospitalière. RéSULTATS: La cohorte comprenait 36 386 personnes et l'âge médian était de 63 ans. Entre 2016 et 2018, le monitorage de la troponine a été réalisé chez 2461 (13 %) des 19 046 patient·es, contre 2398 (14 %) des 17 340 patient·es opéré·es entre 2019 et 2021 (RC, 1,08; IC 95%, 1,02 à 1,15). Les patient·es qui ont bénéficié d'une intervention chirurgicale au cours de la deuxième période présentaient moins de comorbidité cardiovasculaire; le RC ajusté pour le monitorage de la troponine était de 1,14 (IC 95 %, 1,07 à 1,21). Au cours des deux périodes, la troponine était élevée chez 561 (2,9 %) et 470 (2,7 %) patient·es, un IM a été documenté chez 54 (0,3 %) et 36 (0,2 %) patient·es, et 95 (0,5 %) et 73 (0,4 %) patient·es sont décédé·es, respectivement. Après ajustement pour tenir compte des différences initiales au cours des deux périodes, les RC pour l'IM et la mortalité étaient de 0,83 (IC 95 %, 0,54 à 1,27) et de 0,88 (IC 95 %, 0,64 à 1,19), respectivement. CONCLUSION: Bien que les probabilités de commande de troponine aient été légèrement mais significativement plus élevées après la publication des lignes directrices de la SCC, les probabilités de détection d'un IM et de mortalité n'ont pas changé.

Gastric variceal bleeding as a form of presentation of a pancreatic neuroendocrine tumor.

NETs (neuroendocrine tumors) constitute a heterogeneous group of epithelial-type neoplasms with a predominantly neuroendocrine differentiation. Although the most common locations are the pancreas, digestive tract, and lung, this type of neoplasm can arise in virtually any organ in the body. They are rare tumors with a wide variety of clinical presentations. Symptomatic tumors are more frequent in younger patients and present at more advanced pathological stages. We present the case of a 42-year-old male with idiopathic splenomegaly and bicytopenia (anaemia and thrombocytopenia) under study by haematology department who was admitted due to an episode of melena and hemoglobin of 4.5 mg/dl. Isolated gastric varices (IGV1) with red spots were confirmed at gastroscopy and endoscopic variceal obturation using cyanoacrylate was performed in two sessions. An endoscopic ultrasonography was performed, showing thrombosis of the splenic vein extending towards the splenoportal confluence with anechoic serpiginous structures outside and inside the gastric wall suggestive of collateral circulation with gastric varices (GV). An increase in portal caliber was observed, with no signs of liver cirrhosis. Computed tomography confirms the findings. Two months/week/days later he was readmitted with rebleeding signs after starting anticoagulant treatment, so it was decided to perform a splenectomy due to failure of the endoscopic treatment. Histology revealed infiltration of the spleen by a well-differentiated neuroendocrine tumor (NET). Gallium PET/CT and Octreotid scan showed uptake in the body and tail of the pancreas with positivity for somatostatin receptors previously undetected by other means. Finally, treatment was completed with distal pancreatectomy and splenoportal axis trombectomy with vascular esplenic resection and the patient was discharged from hospital.

Increasing Social Connectedness for Underserved Older Adults Living With Depression: A Pre-Post Evaluation of PEARLS.

OBJECTIVE: To evaluate PEARLS effectiveness for increasing social connectedness among underserved older adults with depression. DESIGN: Multisite, pre-post single-group evaluation. SETTING: Community-based social service organizations (N = 16) in five U.S. states, purposively sampled for maximum variation of participants and providers. PARTICIPANTS: A total of 320 homebound older adults (mean(SD) age 72.9(9.6), 79% female, 44% people of color, 81% low-income, 61% living alone, average four chronic conditions) with clinically significant depression (PHQ-9 mean(SD) 12.7(4.6)). INTERVENTION: Four to 6 month home-based depression care management model delivered by trained front-line providers. MEASUREMENTS: Brief validated social connectedness scales: Duke Social Support Index 10-item (DSSI-10), PROMIS-Social Isolation (6-item), UCLA-Loneliness (3-item); sociodemographic and health measures. RESULTS: At baseline, PEARLS participants overall and with ≥1 of the following characteristics were less socially connected: younger (50-64), white, LGBTQ+, not partnered, not caregiving, living alone, financial limitations, chronic conditions, and/or recently hospitalized. Six-months post-PEARLS enrollment, participants significantly increased social interactions and satisfaction with social support (DSSI-10 t[312] = 5.2, p <0.001); and reduced perceived isolation (PROMIS t[310] = 6.3, p <0.001); and loneliness (UCLA t[301] = 3.7, p =0.002), with small to moderate effect sizes (Cohen's d DSSI-10: 0.28, PROMIS-SI: 0.35, UCLA: 0.21). Increased social connectedness was associated with reduced depression. Improvements in social connectedness (except social interactions) persisted during early COVID-19. Being Latino and/or having difficulty paying for basic needs was associated with less improvement in post-PEARLS social connectedness. CONCLUSION: PEARLS has potential to improve social connectedness among underserved older adults, though additional supports may be needed for persons facing multiple social determinants of health. Further research is needed to establish causality.

Towards the elimination of hepatitis C: implementation of reflex testing in Andalusia.

BACKGROUND AND AIM: undiagnosed hepatitis C virus (HCV) infection and/or inadequate access to care are barriers to the elimination of HCV. Reflex testing has proven to facilitate referral to care, treatment and viral elimination. In this study, a reflex testing program was implemented in Andalusia and its impact on access to care was evaluated. PATIENTS AND METHODS: an observational, retrospective and prospective study was performed across diagnostic laboratories responsible for HCV diagnosis in southern Spain. After surveying the barriers to performing reflex testing, the number of patients that were not referred for care in 2016 was retrospectively studied (pre-reflex cohort). Subsequently, several measures were proposed to overcome the identified barriers. Finally, reflex testing was implemented and its impact evaluated. RESULTS: the pre-reflex cohort included information from 1,053 patients. Slightly more than half of the patients (n = 580; 55%) visited a specialist for treatment evaluation during a median period of 71 days (interquartile range = 35-134) since the date of diagnosis. The post-reflex cohort (September 2017 to March 2018) included 623 patients. Only 17% (n = 106) of the patients had not been referred for care or evaluated for treatment in a median period of 52 days (interquartile range = 28-86). CONCLUSIONS: in 2016, nearly half of new HCV diagnoses in southern Spain were not referred for care. Barriers to the implementation of reflex testing were overcome in our study. Moreover, this strategy was effectively implemented in 2017. Reflex testing contributed to improving referral for care. This program will contribute to the micro-elimination of hepatitis C in Spain.

MIC of amoxicillin/clavulanate according to CLSI and EUCAST: discrepancies and clinical impact in patients with bloodstream infections due to Enterobacteriaceae.

Objectives: To compare results of amoxicillin/clavulanate susceptibility testing using CLSI and EUCAST methodologies and to evaluate their impact on outcome in patients with bacteraemia caused by Enterobacteriaceae. Patients and methods: A prospective observational cohort study was conducted in 13 Spanish hospitals. Patients with bacteraemia due to Enterobacteriaceae who received empirical intravenous amoxicillin/clavulanate treatment for at least 48 h were included. MICs were determined following CLSI and EUCAST recommendations. Outcome variables were: failure at the end of treatment with amoxicillin/clavulanate (FEAMC); failure at day 21; and 30 day mortality. Classification and regression tree (CART) analysis and logistic regression were performed. Results: Overall, 264 episodes were included; the urinary tract was the most common source (64.7%) and Escherichia coli the most frequent pathogen (76.5%). Fifty-two isolates (19.7%) showed resistance according to CLSI and 141 (53.4%) according to EUCAST. The kappa index for the concordance between the results of both committees was only 0.24. EUCAST-derived, but not CLSI-derived, MICs were associated with failure when considered as continuous variables. CART analysis suggested a 'resistance' breakpoint of > 8/4 mg/L for CLSI-derived MICs; it predicted FEAMC in adjusted analysis (OR = 1.96; 95% CI: 0.98-3.90). Isolates with EUCAST-derived MICs >16/2 mg/L independently predicted FEAMC (OR = 2.10; 95% CI: 1.05-4.21) and failure at day 21 (OR= 3.01; 95% CI: 0.93-9.67). MICs >32/2 mg/L were only predictive of failure among patients with bacteraemia from urinary or biliary tract sources. Conclusions: CLSI and EUCAST methodologies showed low agreement for determining the MIC of amoxicillin/clavulanate. EUCAST-derived MICs seemed more predictive of failure than CLSI-derived ones. EUCAST-derived MICs >16/2 mg/L were independently associated with therapeutic failure.

Impact of the MIC of piperacillin/tazobactam on the outcome for patients with bacteraemia due to Enterobacteriaceae: the Bacteraemia-MIC project.

OBJECTIVE: Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial. PATIENTS AND METHODS: A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6). CONCLUSIONS: We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.

Secondary fracture prevention in Spanish primary care: results of the PREFRAOS Study.

This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who do receive treatment, and more than one-quarter having no follow-up visits post-fracture. These data highlight the need to improve secondary fracture prevention in primary care. PURPOSE: To describe osteoporosis (OP) treatment patterns and follow-up in subjects with fragility fracture seen in Spanish primary care (PC). METHODS: This observational, retrospective chart review included subjects aged ≥ 70 years listed in the centers' records (November 2018 to March 2020), with ≥ 1 fragility fracture and prior consultation for any reason; subjects who had participated in another study were excluded. Outcomes included OP treatments and follow-up visits post-fragility fracture. RESULTS: Of 665 subjects included, most (87%) were women; overall mean (SD) age, 82 years. Fewer than two thirds (61%) had received any prior OP treatment (women, 65%; men, 38%); of these, 38% had received > 1 treatment (women, 25%; men, 13%). Among treated subjects, the most frequent first-line treatments were alendronate (43%) and RANKL inhibitor denosumab (22%), with a higher discontinuation rate and shorter treatment duration observed for alendronate (discontinuation, 42% vs 16%; median treatment duration, 2.5 vs 2.1 years). Over one-quarter (26%) of subjects had no follow-up visits post-fragility fracture, with this gap higher in women than men (35% versus 25%). The most common schedule of follow-up visits was yearly (43% of subjects with a fragility fracture), followed by half-yearly (17%) and biennial (10%), with a similar trend in men and women. Most OP treatments were prescribed by PC physicians, other than teriparatide and zoledronate. CONCLUSIONS: Across Spanish PC, we observed a large gap in the treatment and follow-up of elderly subjects experiencing a fragility fracture. Our data highlights the urgent need to improve secondary fracture prevention in PC.

Cerebroprotective Effects of the TLR4-Binding DNA Aptamer ApTOLL in a Rat Model of Ischemic Stroke and Thrombectomy Recanalization.

ApTOLL, a TLR4 modulator aptamer, has demonstrated cerebroprotective effects in a permanent ischemic stroke mouse model, as well as safety and efficacy in early phase clinical trials. We carried out reverse translation research according to STAIR recommendations to further characterize the effects and mechanisms of ApTOLL after transient ischemic stroke in rats and to better inform the design of pivotal clinical trials. Adult male rats subjected to transient middle cerebral artery occlusion were treated either with ApTOLL or the vehicle intravenously at different doses and time-points. ApTOLL was compared with TAK-242 (a TLR4 inhibitor). Female rats were also studied. After neurofunctional evaluation, brains were removed for infarct/edema volume, hemorrhagic transformation, and histologic determinations. Peripheral leukocyte populations were assessed via flow cytometry. ApTOLL showed U-shaped dose-dependent cerebroprotective effects. The maximum effective dose (0.45 mg/kg) was cerebroprotective when given both before reperfusion and up to 12 h after reperfusion and reduced the hemorrhagic risk. Similar effects occurred in female rats. Both research and clinical ApTOLL batches induced slightly superior cerebroprotection when compared with TAK-242. Finally, ApTOLL modulated circulating leukocyte levels, reached the brain ischemic tissue to bind resident and infiltrated cell types, and reduced the neutrophil density. These results show the cerebroprotective effects of ApTOLL in ischemic stroke by reducing the infarct/edema volume, neurofunctional impairment, and hemorrhagic risk, as well as the peripheral and local immune response. They provide information about ApTOLL dose effects and its therapeutic time window and target population, as well as its mode of action, which should be considered in the design of pivotal clinical trials.

Synthesis of enantioenriched tertiary boronic esters by the lithiation/borylation of secondary alkyl benzoates.

Simple, secondary 2,4,6-triisopropyl benzoates (TIB esters) and secondary dialkyl N,N-diisopropyl carbamates have been reported to be resistant to deprotonation by strong bases. We have found that the combination of sBuLi (1.6 equiv) and TMEDA (6 equiv) in CPME at -60 °C enables deprotonation of unactivated secondary dialkyl TIB esters, but not the carbamates. These carbanions were reacted with a range of neopentyl boronic esters which, after 1,2-metalate rearrangement and oxidation, gave a range of tertiary alcohols in high yield and universally high er. Further functional group transformations of the tertiary boronic esters were demonstrated (conversion to quaternary centers, C-tertiary amines) together with application of the methodology to the synthesis of the simplest unbranched hydrocarbon bearing a quaternary center, (R)-4-ethyl-4-methyloctane, validating the synthetic utility of the methodology.

Role of norovirus in acute gastroenteritis in the Northwest of Spain during 2010-2011.

A total of 2,643 samples from patients with gastroenteritis in Galicia (NW Spain) were tested for the presence of Norovirus (NoV). NoV genogroup GI was detected in 416 (15.7%) samples, while NoV genogroup GII was detected in 278 (10.5%) samples. Mixed infections of NoV GI and GII were observed in 53 (2%) samples. Total prevalence of NoV in the analyzed samples was 28.3%. Besides NoV diagnosis assay, all the specimens were also submitted to routine clinical bacteriology tests. Cryptosporidium spp. as well as adenovirus (AdV) and rotavirus (RV) were determined on some samples after specific request by hospital units. The results obtained allowed to determine the disease etiology in 14.4% of the patients. Taking into account all the microorganisms studied, the etiological agent was determined for 39.5% of the cases. The results indicated that NoVs are the leading cause of acute gastroenteritis in all age-groups in Northwestern Spain, and that the lack of routine NoV diagnosis contributes to the underestimation of the importance of this virus, not only in outbreaks, but also in sporadic cases of acute gastroenteritis.

Anticipatory Antifungal Treatment in Critically Ill Patients with SARS-CoV-2 Pneumonia.

BACKGROUND: The aim of this study was to investigate the incidence of COVID-19-associated pulmonary aspergillosis (CAPA) in critically ill patients and the impact of anticipatory antifungal treatment on the incidence of CAPA in critically ill patients. METHODS: Before/after observational study in a mixed intensive care unit (ICU) of a university teaching hospital. The study took place between March 2020 and June 2022. Inclusion criteria were critically ill patients with severe SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Two analysis periods were compared according to whether or not antifungal therapy was given early. RESULTS: A total of 160 patients with severe SARS-CoV-2 pneumonia and invasive mechanical ventilation were included. The incidence of CAPA in the first study period was 19 out of 58 patients (32.75%); during the second period, after implementation of the intervention (anticipatory antifungal therapy), the incidence of CAPA decreased to 10.78% (11 out of 102 patients). In patients with CAPA under invasive mechanical ventilation, the mortality rate decreased from 100% to 64%. CONCLUSIONS: Anticipating antifungal treatment in patients with SARS-CoV-2 pneumonia under invasive mechanical ventilation was associated with a decrease in the incidence and mortality of pulmonary aspergillosis.

Synthesis of benzopolycyclic cage amines: NMDA receptor antagonist, trypanocidal and antiviral activities.

The synthesis of several 6,7,8,9,10,11-hexahydro-9-methyl-5,7:9,11-dimethano-5H-benzocyclononen-7-amines is reported. Several of them display low micromolar NMDA receptor antagonist and/or trypanocidal activities. Two compounds are endowed with micromolar anti vesicular stomatitis virus activity, while only one compound shows micromolar anti-influenza activity. The anti-influenza activity of this compound does not seem to be mediated by blocking of the M2 protein.

Evaluating the message of an ongoing communication campaign to reduce the duration of untreated psychosis in a Latinx community in the United States.

AIM: Initiatives aimed at reducing the duration of untreated psychosis (DUP) attempt to increase the community's level of psychosis literacy. Most of these efforts, however, have failed to reduce DUP. One plausible explanation is that the campaigns do not actually increase psychosis literacy. To date, there have been few efforts to assess whether the campaign messaging does indeed increase psychosis literacy prior to or during the campaign. This study evaluated whether the message of the La CLAve DUP reduction program delivered during the campaign increased the psychosis literacy of a U.S. Latinx community. METHODS: The sample consisted of 81 Latinx community residents aged 15-84. Two community health educators of the La CLAve campaign facilitated workshops using a narrative film to initiate a conversation in the community about the signs of psychosis and the importance of professional help-seeking early in the illness course. Psychosis literacy was assessed via questionnaires pertaining to a hypothetical vignette administered before and after the workshops. RESULTS: The psychosis literacy of participants increased after the workshops in several domains. Participants' knowledge of multiple psychotic symptoms, self-efficacy in their ability to recognize psychosis in others, and correct attributions of a hypothetical vignette's psychotic symptoms significantly increased. No changes were observed in recommendations for professional help-seeking. CONCLUSIONS: These findings provide support for the effectiveness of the La CLAve messaging in increasing psychosis literacy of U.S. Latinx community residents. Evidence-based campaign messaging is needed to increase the success of DUP reduction programs especially among underserved communities.

Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic.

Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.

New oxapolycyclic cage amines with NMDA receptor antagonist and trypanocidal activities.

The synthesis of several (1,2,3,5,6,7-hexahydro-1,5:3,7-dimethano-4-benzoxonin-3-yl)amines and related compounds is reported. Several of them display very similar activity to memantine as NMDA receptor antagonists. Several derivatives showed a significant level of trypanocidal activity.

[Serological markers in immigrant and Spanish pregnant women in Granada]. / Marcadores serológicos en gestantes inmigrantes y autóctonas en Granada.

INTRODUCTION: Female immigration from less developed countries into Spain has grown in number over the years, and could contribute to changing the prevalence of routine serological markers in pregnant women. MATERIAL AND METHODS: From April 2007 until May 2008 we studied the prevalence of serum antibodies against Treponema pallidum, Toxoplasma gondii, rubella virus, human immunodeficiency virus (HIV 1/2), and hepatitis B virus (HBV) in samples from 4,171 immigrant and Spanish pregnant women in Granada. RESULTS: The seroprevalence of toxoplasmosis in pregnant immigrants was higher than in non-immigrants (44% vs. 14.4%). The overall prevalence against rubella was 97.3%. Sub-Saharan and North African women showed the lowest prevalence (88% and 89%). The prevalence of HBsAg was higher in immigrants than in Spanish women (2.6% vs. 0.4%), and especially high among the Eastern European (6.9%) and Asian (8.1%) pregnant women. The seroprevalences of HIV (0.9% vs. 0.1%) and syphilis (TPHA) (3.5% vs. 0.07%), were higher in immigrants. Seroprevalence against T. pallidum was higher among Eastern European (11.5%) and Latin-American (3.5%) women, whereas sub-Saharan (11.8%) and North African (1%) women showed the highest anti-HIV prevalence. CONCLUSION: Hepatitis B, anti-HIV, syphilis, and antibodies against T. gondii are found more frequently in immigrants than in Spanish pregnant women, whereas rubella protection in Spanish women is higher than immigrant pregnant women.

Sample pooling for SARS-CoV-2 RT-PCR screening.

OBJECTIVE: To evaluate the efficacy of sample pooling compared to the individual analysis for the diagnosis of coronavirus disease 2019 (COVID-19) by using different commercial platforms for nucleic acid extraction and amplification. METHODS: A total of 3519 nasopharyngeal samples received at nine Spanish clinical microbiology laboratories were processed individually and in pools (342 pools of ten samples and 11 pools of nine samples) according to the existing methodology in place at each centre. RESULTS: We found that 253 pools (2519 samples) were negative and 99 pools (990 samples) were positive; with 241 positive samples (6.85%), our pooling strategy would have saved 2167 PCR tests. For 29 pools (made out of 290 samples), we found discordant results when compared to their correspondent individual samples, as follows: in 22 of 29 pools (28 samples), minor discordances were found; for seven pools (7 samples), we found major discordances. Sensitivity, specificity and positive and negative predictive values for pooling were 97.10% (95% confidence interval (CI), 94.11-98.82), 100%, 100% and 99.79% (95% CI, 99.56-99.90) respectively; accuracy was 99.80% (95% CI, 99.59-99.92), and the kappa concordant coefficient was 0.984. The dilution of samples in our pooling strategy resulted in a median loss of 2.87 (95% CI, 2.46-3.28) cycle threshold (Ct) for E gene, 3.36 (95% CI, 2.89-3.85) Ct for the RdRP gene and 2.99 (95% CI, 2.56-3.43) Ct for the N gene. CONCLUSIONS: We found a high efficiency of pooling strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA testing across different RNA extraction and amplification platforms, with excellent performance in terms of sensitivity, specificity and positive and negative predictive values.

Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.

OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.

Endothelin-1-Mediated Drug Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.

Progression on therapy in non-small cell lung carcinoma (NSCLC) is often evaluated radiographically, however, image-based evaluation of said therapies may not distinguish disease progression due to intrinsic tumor drug resistance or inefficient tumor penetration of the drugs. Here we report that the inhibition of mutated EGFR promotes the secretion of a potent vasoconstrictor, endothelin-1 (EDN1), which continues to increase as the cells become resistant with a mesenchymal phenotype. As EDN1 and its receptor (EDNR) is linked to cancer progression, EDNR-antagonists have been evaluated in several clinical trials with disappointing results. These trials were based on a hypothesis that the EDN1-EDNR axis activates the MAPK-ERK signaling pathway that is vital to the cancer cell survival; the trials were not designed to evaluate the impact of tumor-derived EDN1 in modifying tumor microenvironment or contributing to drug resistance. Ectopic overexpression of EDN1 in cells with mutated EGFR resulted in poor drug delivery and retarded growth in vivo but not in vitro. Intratumoral injection of recombinant EDN significantly reduced blood flow and subsequent gefitinib accumulation in xenografted EGFR-mutant tumors. Furthermore, depletion of EDN1 or the use of endothelin receptor inhibitors bosentan and ambrisentan improved drug penetration into tumors and restored blood flow in tumor-associated vasculature. Correlatively, these results describe a simplistic endogenous yet previously unrealized resistance mechanism inherent to a subset of EGFR-mutant NSCLC to attenuate tyrosine kinase inhibitor delivery to the tumors by limiting drug-carrying blood flow and the drug concentration in tumors. SIGNIFICANCE: EDNR antagonists can be repurposed to improve drug delivery in VEGFA-secreting tumors, which normally respond to TKI treatment by secreting EDN1, promoting vasoconstriction, and limiting blood and drug delivery.

Comparison of different methods of determining beta-lactam susceptibility in clinical strains of Pseudomonas aeruginosa.

One hundred and one randomly selected (2003-2005) clinical isolates of Pseudomonas aeruginosa were used to assess the quantitative (MIC) and qualitative (susceptibility category) agreement between the microdilution broth reference method (RM) and disc diffusion (DD), Etest and the VITEK 2 automated susceptibility test system for determination of the susceptibility of P. aeruginosa to piperacillin (PIP), PIP-tazobactam (TZP), ceftazidime (CAZ), aztreonam (ATM) cefepime (FEP) and imipenem (IMP). The results obtained by the RM were compared with those obtained by the other methods. The RM and DD were performed according to CLSI criteria. Etest and VITEK 2 were according to the manufacturer's instructions. The Advanced Expert System (AES), which interprets MICs generated by VITEK 2, was modified with new rules of interpretation. Overall, VITEK 2 showed the lowest MIC90 values for the six antibiotics. The RM categorical testing (susceptibility and resistance) rates with P. aeruginosa were 11.8 and 88.1 for PIP, 22.7 and 77.2 for TZP, 14.8 and 78.2 for CAZ, 12.8 and 54.4 for ATM, 16.8 and 75.3 for FEP, and 7.9 and 90.1 for IMP, respectively. Very major errors (false susceptible) were only detected for ATM and FEP with DD and for IMP with three methods. Major errors (false resistant) were generally acceptable for all antibiotics except TZP. VITEK 2 yielded a high level of minor errors (trends toward false susceptibility), mainly with CAZ and FEP. A good agreement was obtained for all antibiotics/methods assayed, thus highlighting the importance of the AES for categorization of beta-lactam susceptibility in P. aeruginosa.