Relationship between immunosuppression and intensive care unit-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter cohort study.

PURPOSE: The impact of immunosuppression on intensive care unit (ICU)-acquired colonization and infection related to multidrug-resistant (MDR) bacteria (ICU-MDR-col and ICU-MDR-inf, respectively) is unknown. METHODS: We carried out an observational prospective cohort study in 8 ICUs in France (all with single-bed rooms and similar organizational characteristics). All consecutive patients with an ICU stay > 48 h were included, regardless of immune status, and followed for 28 days. Patients underwent systematic screening for colonization with MDR bacteria upon admission and every week subsequently. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, solid-organ transplant, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic. The primary endpoint was the incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. RESULTS: 750 patients (65.9% males, median age 65 years) were included, among whom 264 (35.2%) were immunocompromised. Reasons for ICU admission, severity scores and exposure to invasive devices and antibiotics during ICU stay were comparable between groups. After adjustment for center and pre-specified baseline confounders, immunocompromised patients had a lower incidence rate of ICU-MDR-col and/or ICU-MDR-inf (adjusted incidence ratio 0.68, 95% CI 0.52-0.91). When considered separately, the difference was significant for ICU-MDR-col, but not for ICU-MDR-inf. The distribution of MDR bacteria was comparable between groups, with a majority of Enterobacteriacae resistant to third-generation cephalosporins (~ 74%). CONCLUSION: Immunocompromised patients had a significantly lower incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. This finding points to the role of contact precautions and isolation measures, and could have important implications on antibiotic stewardship in this population.

Mapping and Crosswalk of the Oxford Hip Score and Different Versions of the Hip Disability and Osteoarthritis Outcome Score.

BACKGROUND: Patient-reported outcome measures such as the Oxford-12 Hip Score and Hip Disability and Osteoarthritis Outcome Score (HOOS) are used in daily orthopaedic practice to evaluate patients. Because different studies use different scores, it would be important to build conversion tables between scores (crosswalk) to compare the results of one study with those of another study. Various mapping methods can be used to develop crosswalk tables that convert Oxford-12 scores to the HOOS (and its derivatives, including the HOOS physical function short form, HOOS joint replacement, and HOOS-12) and vice versa. Although prior studies have investigated this issue, they are limited to short forms of the HOOS score. Consequently, they cannot be applied to hip preservation surgery and do not include quality-of-life items, whereas the Oxford-12 Hip Score is used for all hip evaluations. QUESTIONS/PURPOSES: We prospectively studied the Oxford-12 and HOOS and its derivatives to (1) determine which version of the HOOS has the best mapping with the Oxford-12, (2) define the most-appropriate mapping method using selected indicators, and (3) generate crosswalk tables between these two patient-reported outcome measures. METHODS: The study enrolled 500 adult patients before primary THA (59% men [294 of 500 patients]) with hip osteoarthritis or avascular necrosis of the femoral head who completed the HOOS and Oxford-12. Patients were recruited from January 2018 to September 2019 in a tertiary-care university hospital, and we included all primary THAs in patients older than 18 years with a BMI lower than 35 kg/m2 and greater than 18 kg/m2. After a minimum of 6 months of follow-up, 39% (195 of 500) of the patients were assessed using the same tools. To determine which version of the HOOS mapped best to the Oxford-12 and what the most-appropriate mapping method was, we used preoperative data from all 500 patients. Because there is no consensus on the method to establish crosswalk, various mapping methods (linear regression, tobit regression, and quantile regression) and equating methods (linear equating and equipercentile method) were applied along with cross-validation to determine which method was the most suitable and which form of the HOOS provided the best result according to different criteria (mean absolute error, r2, and Kolmogorov-Smirnov distance).To generate crosswalk tables, we created a conversion table (between the Oxford-12 and the HOOS form that was chosen after answering our first research question and the method chosen after answering our second question) using preoperative and postoperative data (n = 695). This table was meant to be simple to use and allows easy conversions from one scoring system to another. RESULTS: The Oxford-12 and HOOS were strongly correlated (Pearson correlation coefficient range 0.586-0.842) for the HOOS subcategories and HOOS physical function, HOOS joint replacement, and HOOS-12. The correlation between the HOOS-12 and Oxford-12 was the strongest (r = 0.825). According to the three different criteria and five methods, the HOOS-12 was the best suited for mapping. The goal was to minimize the mean absolute error (perfect model = 0), have a Kolmogorov-Smirnov distance as close as possible to 0, and have the r2 as close as possible to 1. Regarding the most-suitable method for the crosswalk mapping (research question 2), the five methods generated similar results for the r2 (range 0.63-0.67) and mean absolute error (range 6-6.2). For the Kolmogorov-Smirnov distance, the equipercentile method was the best (Kolmogorov-Smirnov distance 0.04), with distance reduced by 43% relative to the regression methods (Kolmogorov-Smirnov distance 0.07). A graphical comparison of the predicted and observed scores showed that the equipercentile method provided perfect superposition of predicted and observed values after mapping. Finally, crosswalk tables were produced between the HOOS-12 and Oxford-12. CONCLUSION: The HOOS-12 is the most complete and suitable form of the HOOS for mapping with the Oxford-12, while the equipercentile method is the most suitable for predicting values after mapping. This study provides clinicians with a reliable tool to crosswalk between these scores not only for joint arthroplasty but also for all types of hip surgeries while also assessing quality of life. Our findings should be confirmed in additional studies. CLINICAL RELEVANCE: The resulting crosswalk tables can be used in meta-analyses, systematic reviews, or clinical practice to compare clinical studies that did not include both outcome scores. In addition, with these tools, the clinician can collect only one score while still being able to compare his or her results with those obtained in other databases and registries, and to add his or her results to other databases and joint registries.

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG's antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

Can the minimal clinically important difference be determined in a French-speaking population with primary hip replacement using one PROM item and the Anchor strategy?

BACKGROUND: The impact of surgery on the patient is classically assessed on pre- and post-treatment scores. However, it is increasingly recommended to rank these results according to the minimal clinically important difference (MCID), using either the data distribution method or the anchor method, latter consisting in an extra question specifically targeting the patient's improvement. MCIDs vary between populations and, to the best of our knowledge; there have been no investigations in France regarding this in the context of total hip replacement (THR). Therefore, we conducted a prospective study in a population with THR to determine: 1) whether MCID scores in France were comparable to those reported in the data from the international literature; 2) whether a general item taken from a different score could serve as an anchor; and 3) whether an item from the actual questionnaire itself could serve as an anchor. HYPOTHESIS: When pre- and post-treatment scores are available, an item from the questionnaire itself can serve as an anchor for MCID. MATERIAL AND METHODS: In a prospective observational study, 123 primary THR patients (69 male, 54 female), out of 150 initially included, completed the 5 domains of the HOOS hip disability and osteoarthritis outcome score and the Oxford-12 questionnaire, preoperatively and at 6-12 months. The MCID was calculated via the distribution-based and the anchor-based methods. Two Oxford items (questions 1 and 2) and 2 HOOS items (questions S1 and Q4) were used as anchors, as well as a supplementary question on improvement and the Forgotten Joint Score (FJS). RESULTS: At a mean 10.12±1.2 months' follow-up [range, 6.5-11.9 months], the Oxford-12 score increased from 19±8 [3-35] to 40±10 [8-48] (p<0.001), all HOOS components demonstrated improvement, and the FJS at the final follow-up was 71±29 [0-100]. The general items (Oxford question 1 and HOOS question Q4) were more discriminating than the joint-specific items (Oxford question 2 and HOOS question S1). Based on results from the 3 anchors (improvement rated 1 to 5, Oxford question 1 and HOOS question Q4), 3 to 5 patients showed deterioration, 5 to 6 were unchanged, 30 to 40 were slightly improved, and 73 to 80 were improved by THR. The mean MCID on both distribution and anchor methods was 9 [5.5-12] for Oxford-12, 20 [12-27] for HOOS symptoms, 26 [10-36] for HOOS pain, 22 [11.5-28] for HOOS function, 26 [13-34] for HOOS sport and 22 [14-28] for HOOS quality of life. DISCUSSION: The MCID for the Oxford-12 and HOOS scores in a French population was comparable to data from the past literature. Using a score item as an anchor to define improvement is possible, but only if a general item is used. LEVEL OF EVIDENCE: IV; prospective study without control group. CLINICAL TRIALS REGISTRATION: NCT04057651.

Does change in language change the properties of a shortened score previously validated in its complete version? Validation of the French versions of the HOOS-12 and KOOS-12 scores in primary knee and hip arthroplasties.

BACKGROUND: The HOOS and KOOS scoring questionnaires comprise respectively 40 and 42 items; a shorter 12-item version was recently developed, but remains to be validated in a French-speaking population. We therefore conducted a prospective study: 1) to determine whether the new 12-item versions in French are equivalent to the longer HOOS and KOOS versions, and 2) to validate the French-language HOOS-12 and KOOS-12 patient-reported outcome measures in a population of primary total hip and knee arthroplasty: validity, reliability, and responsiveness. HYPOTHESIS: The change in language in a score already validated in its long version does not alter its properties in the short version. MATERIAL AND METHODS: One hundred patients (59 males, 41 females) undergoing primary total hip arthroplasty and 100 patients (43 males, 57 females) undergoing primary total knee arthroplasty were prospectively included. They filled out the original HOOS or KOOS questionnaires, their simplified versions (PS: Physical function Short form; JR: Joint Replacement) and the short HOOS-12 and KOOS-12 versions, and also the Oxford-12 score assessing the affected joint, preoperatively, then at 6-12 months. RESULTS: The 100% response rate confirmed ease of use. There were no redundant items. There were strong correlations between the 12-item and longer versions (>0.9). The HOOS-12 and KOOS-12 scores were reliable and valid: 1) there were no ceiling or floor effects for pre- or postoperative KOOS-12 scores, although a ceiling effect was found for HOOS-12 postoperatively (20% of patients having maximum scores of 100); 2) internal consistency was confirmed, with Cronbach alpha>0.8; 3) external consistency between Oxford-12 and HOOS-12/KOOS-12 was excellent, with Pearson correlation coefficient>0.8. Sensitivity to pre-/postoperative change was confirmed, with effect size>0.8. DISCUSSION: The present study confirmed the usefulness of this new 12-item form for HOOS and KOOS. Properties were identical between the French- and English-language versions, authorising everyday use of these simpler versions. LEVEL OF EVIDENCE: IV; prospective study without control group.

Incidence and Predictive Factors of Postprandial Hyperinsulinemic Hypoglycemia After Roux-en-Y Gastric Bypass: A Five year Longitudinal Study.

BACKGROUND: Postprandial hyperinsulinemic hypoglycemia (PHH) is often reported after Roux-en-Y gastric bypass (RYGB). In the absence of a prospective study, the clinical and biological determinants of PHH remain unclear. OBJECTIVE: To determine the incidence and predictive factors of PHH after RYGB. METHODS: Participants were 957 RYGB patients enrolled in an ongoing longitudinal cohort study. We analyzed the results of an oral glucose tolerance test (OGTT) routinely performed before surgery and 1 and/or 5 years after. PHH was defined as blood glucose < 50 mg/dL AND plasma insulin > 3 mU/L at 120 minutes post glucose challenge. Validated indices of insulin sensitivity (Matsuda index), beta-cell function (Insulinogenic index), and beta-cell mass (fasting C-peptide: glucose ratio) were calculated, from glucose, insulin, and c-peptide values measured during OGTT. RESULTS: OGTT results were available in all patients at baseline, in 85.6% at 12 months and 52.8% at 60 months. The incidence of PHH was 0.5% at baseline, 9.1% * and 7.9%* at 12 months and 60 months following RYGB (*: P < 0.001). In multivariate logistic regression analysis, PHH after RYGB was independently associated with lower age (P = 0.005), greater weight loss (P = 0.031), as well as higher beta-cell function (P = 0.002) and insulin sensitivity (P < 0.001), but not with beta-cell mass (P = 0.381). A preoperative elevated beta-cell function was an independent predictor of PHH after RYGB (receiver operating characteristics curve area under the curve 0.68, P = 0.04). CONCLUSIONS:: The incidence of PHH significantly increased after RYGB but remained stable between 1 and 5 years. The estimation of beta-cell function with an OGTT before surgery can identify patients at risk for developing PHH after RYGB.

PASE: a web-based platform for peptide/protein microarray experiments.

Peptide microarray technology requires bioinformatics and statistical tools to manage, store, and analyze the large amount of data produced. To address these needs, we developed a system called protein array software environment (PASE) that provides an integrated framework to manage and analyze microarray information from polypeptide chip technologies.