A Semiquantitative Protein-Fragment Complementation Assay to Study Protein-Protein Interactions of the Polymerase Complex in Cellula.

Protein-fragment complementation assays (PCAs) are powerful tools to investigate protein-protein interactions in a cellular context. These are especially useful to study unstable proteins and weak interactions that may not resist protein isolation or purification. The PCA based on the reconstitution of the Gaussia princeps luciferase (split-luc) is a sensitive approach allowing the mapping of protein-protein interactions and the semiquantitative measurement of binding affinity. Here, we describe the split-luc protocol we used to map the viral interactome of measles virus polymerase complex.

Bilateral spheno-orbital meningiomas: surgical management, progression, and recurrence.

OBJECTIVE: Bilateral spheno-orbital meningiomas (bSOMs) are a rare entity among meningiomas. These tumors are benign and predominantly affect women. They represent 4% of spheno-orbital meningiomas (SOMs) and are poorly described in the literature. This study aimed to describe the characteristics, risk factors, evolution, and management of bSOMs. METHODS: Twenty patients with bSOMs were enrolled in a multicentric descriptive study including 15 neurosurgical departments. RESULTS: In this study, the authors found that bSOMs affected exclusively women, with a mean age of 50 years. Approximately 65% of patients were on progestin therapy. The mean follow-up in this series was 55 months. Clinically, visual symptoms were predominant: proptosis was present in 17 of 20 patients (85%; 7 unilateral, 10 bilateral), and a decrease in visual acuity was observed in 11 of 20 patients (55%; 6/10 to 9/10 in 6 patients, 3/10 to 5/10 in 1 patient, and < 3/10 in 4 patients). Contrary to unilateral SOMs, the authors identified that intracranial hypertension was a common presentation (25%) of bSOMs. Surgical management with gross-total resection was the gold standard treatment. Recurrences only occurred following subtotal resection in 36% to 60% of patients, with a median time of 50 to 54 months after surgery. Visual improvement or stability was observed in 75% of cases postoperatively. Progesterone receptor expression levels were 70% to 100% in 10 of 11 (91%) cases. CONCLUSIONS: Bilateral SOMs are usually found in female patients and are strongly associated with hormone replacement therapy. Early surgical management with gross-total resection is the most effective treatment in terms of recurrence and improves visual acuity. Given the slow progressive nature of bSOMs and their time to recurrence, which can be up to 10 years, long-term follow-up of patients is essential.

Evolution of homologous recombination rates across bacteria.

Bacteria are nonsexual organisms but are capable of exchanging DNA at diverse degrees through homologous recombination. Intriguingly, the rates of recombination vary immensely across lineages where some species have been described as purely clonal and others as "quasi-sexual." However, estimating recombination rates has proven a difficult endeavor and estimates often vary substantially across studies. It is unclear whether these variations reflect natural variations across populations or are due to differences in methodologies. Consequently, the impact of recombination on bacterial evolution has not been extensively evaluated and the evolution of recombination rate-as a trait-remains to be accurately described. Here, we developed an approach based on Approximate Bayesian Computation that integrates multiple signals of recombination to estimate recombination rates. We inferred the rate of recombination of 162 bacterial species and one archaeon and tested the robustness of our approach. Our results confirm that recombination rates vary drastically across bacteria; however, we found that recombination rate-as a trait-is conserved in several lineages but evolves rapidly in others. Although some traits are thought to be associated with recombination rate (e.g., GC-content), we found no clear association between genomic or phenotypic traits and recombination rate. Overall, our results provide an overview of recombination rate, its evolution, and its impact on bacterial evolution.

Radiation Proctitis in Patients With Locally Advanced Cervical Cancer Treated by Chemoradiation: Analysis and Predictive Factors From a Retrospective Cohort.

BACKGROUND: Radiation proctitis is a misunderstanding complication of chemoradiation in locally advanced cervical cancer. The objective of our study is to provide a detailed description and analysis of predictive factors associated with radiation proctitis in a retrospective cohort of patients treated by chemoradiation for locally advanced cervical cancer. METHODS: All patients treated by exclusive chemoradiation or chemoradiation followed by brachytherapy for locally advanced cervical cancer from 2011 to 2017 were included in the study. A bivariate analysis was conducted to establish correlations between the occurrence of radiation proctitis and various clinical and technical variables. RESULTS: A total of 128 patients were included in the study. The mean dose (SD) to the planning target volume was 47.1 Gy (6.2). Fifty-nine (46.1%) patients underwent brachytherapy. Sixteen patients (12.5%) developed radiation proctitis, grade 2 or higher in 12 patients (9.3%). In univariate analysis, anticoagulant or antiplatelet treatments (P=0.039), older age (P=0.049), rectal volume irradiated at 40 Gy (P=0.01) and 30 Gy (P=0.037) were significantly associated with the occurrence of a grade ≥2 radiation proctitis. The delivered dose to 2 cm3 of rectum (D2cm3) showed a potential association with the occurrence of radiation proctitis of all grades (P=0.064). CONCLUSION: This study highlights clinical and technical factors that should be considered in assessing the risk of radiation proctitis. These results contribute to a better understanding of this complication.

Are there Still any Benefits to Drainage for Anterior Cervical Arthrodesis/Arthroplasty by Cervicotomy?

STUDY DESIGN: A retrospective single-center study between January 2019 and 2023. OBJECTIVE: The role and contribution of drainage in the anterior approach to the cervical spine (cervicotomy) is much debated, motivated primarily by the prevention of retropharyngeal hematoma, so are there still any benefits to drainage? BACKGROUND: The anterior approach to the cervical spine is a widespread and common procedure performed in almost all spine surgery departments for the replacement of cervical intervertebral discs and medullar or radicular decompression. The primary endpoint was the occurrence of symptomatic postoperative cervical hematoma. METHODS: Four hundred thirty-one patients who had undergone cervical spine surgery by anterior cervicotomy for cervicarthrosis or cervical disc herniation (ACDF, ACDR) were consecutively included. Patients were separated into 2 groups: Group A, 140 patients (with postoperative drainage) and group B, 291 patients (without drainage). RESULTS: Mean follow-up was 2.8 months. The 2 groups were comparable on all criteria, but there was a predominance of arthroplasty (P<0.0001), use of anticoagulants/antiaggregants (P<0.0001) and a greater number of stages (P<0.0001) in group A. There were a total of 4/431 symptomatic postoperative hematomas (0.92%) in this study. Two hematomas occurred in group A (2/140, 1.4%) and two in group B (2/291, 0.68%) (P<0.0001). One patient in group A (0.71%) required surgical drainage for cavity hematoma revealed by marked dyspnea, swallowing and neurological disorders. One case of hematoma diagnosed by dysphonia and neurological deficit was reported in group B (0.34% (P<0.0001). CONCLUSIONS: Placement of a drain during anterior cervicotomy for (ACDF/ACDR) did not limit the occurrence of symptomatic postoperative hematoma.

Impact of metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fracture (pVCF) in neurological and survival prognosis.

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fractures (pVCF) are the most serious debilitating morbidities of spine metastases (SpMs) causing devastating neurological damages. The respective impact of these two metastasis-spreading entities on survival and on neurological damage is debated. METHODS: A French prospective cohort study collected 279 consecutive patients presenting with SpMs between January 2017 and 2021. We compared 174 patients with MESCC and 105 patients with pVCF. RESULTS: The median Overall Survival (OS) for the MESCC group was 13.4 months (SD 1.5) vs 19.2 months (SD 2.3) for pVCF patients (p = 0.085). Sixty-five patients (23.3 %) were operated on: 49/65 (75.4 %) in the MESCC group and 16/65 (15.2 %) in the pVCF group, p < 0.0001. At 6 months FU, in the MESCC group, 21/44 (45.4 %) of non-ambulatory patients at onset improved to ambulatory status (Frankel D-E) vs 10/13 (76.9 %) in the pVCF group (p = 0.007). In multivariable analysis with the Cox proportional hazard model, good ECOG-PS and SINS Score 7-12 [HR: 6.755, 95 % CI 2.40-19.00; p = 0.001] were good prognostic factors for preserved ambulatory neurological status. However, SpMs diagnosed synchronously with the primary tumor [HR: 0.397, 95 % CI 0.185-0.853; p = 0.018] and MESCC [HR: 0.058, 95 % CI 0.107-0.456; p = 0.007] were independent risk factors for impaired neurological function. CONCLUSION: Contrary to pVCF, MESCC causes neurological damage. Nevertheless, neurological recovery remains possible. MESCC and pVCF have no impact on survival. The management of MESCC remains to be clarified and optimized to reduce neurological damage.

Exhaled nitric oxide is associated with inflammatory biomarkers and risk of acute respiratory exacerbations in children with HIV-associated chronic lung disease.

OBJECTIVES: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels. METHODS: Individuals aged 6-19 years with HIV-associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo-controlled randomized trial investigating the effect of 48-week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels. RESULTS: In total, 172 participants were included in this sub-study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow-up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03-1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)-3, -7, and -10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72-1.03, p = 0.103). CONCLUSION: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV-associated chronic lung disease needs further investigation.

Cross-alteration of murine skin and tick microbiome concomitant with pathogen transmission after Ixodes ricinus bite.

BACKGROUND: Ticks are major vectors of diseases affecting humans such as Lyme disease or domestic animals such as anaplasmosis. Cross-alteration of the vertebrate host skin microbiome and the tick microbiome may be essential during the process of tick feeding and for the mechanism of pathogen transmission. However, it has been poorly investigated. METHODS: We used mice bitten by field-collected ticks (nymphs and adult ticks) in different experimental conditions to investigate, by 16S rRNA gene metabarcoding, the impact of blood feeding on both the mouse skin microbiome and the tick microbiome. We also investigated by PCR and 16S rRNA gene metabarcoding, the diversity of microorganisms transmitted to the host during the process of tick bite at the skin interface and the dissemination of the pathogen in host tissues (blood, heart, and spleen). RESULTS: Most of the commensal bacteria present in the skin of control mice were replaced during the blood-feeding process by bacteria originating from the ticks. The microbiome of the ticks was also impacted by the blood feeding. Several pathogens including tick-borne pathogens (Borrelia/Borreliella, Anaplasma, Neoehrlichia, Rickettsia) and opportunistic bacteria (Williamsia) were transmitted to the skin microbiome and some of them disseminated to the blood or spleen of the mice. In the different experiments of this study, skin microbiome alteration and Borrelia/Borreliella transmission were different depending on the tick stages (nymphs or adult female ticks). CONCLUSIONS: Host skin microbiome at the bite site was deeply impacted by the tick bite, to an extent which suggests a role in the tick feeding, in the pathogen transmission, and a potentially important impact on the skin physiopathology. The diversified taxonomic profiles of the tick microbiome were also modified by the blood feeding. Video Abstract.

Impact of Holocene environmental change on the evolutionary ecology of an Arctic top predator.

The Arctic is among the most climatically sensitive environments on Earth, and the disappearance of multiyear sea ice in the Arctic Ocean is predicted within decades. As apex predators, polar bears are sentinel species for addressing the impact of environmental variability on Arctic marine ecosystems. By integrating genomics, isotopic analysis, morphometrics, and ecological modeling, we investigate how Holocene environmental changes affected polar bears around Greenland. We uncover reductions in effective population size coinciding with increases in annual mean sea surface temperature, reduction in sea ice cover, declines in suitable habitat, and shifts in suitable habitat northward. Furthermore, we show that west and east Greenlandic polar bears are morphologically, and ecologically distinct, putatively driven by regional biotic and genetic differences. Together, we provide insights into the vulnerability of polar bears to environmental change and how the Arctic marine ecosystem plays a vital role in shaping the evolutionary and ecological trajectories of its inhabitants.

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre.

PURPOSE: Ultra-hypofractionation breast radiotherapy is a safe alternative to moderate hypofractionation. This study reports the results of two ultrahypofractionated regimens used in clinical practice in a high-volume radiotherapy center in terms of efficacy and of tolerance. METHODS: we included all patients treated in an adjuvant setting with five fractions after breast conserving surgery (BCS), for a histologically-confirmed invasive or in situ breast carcinoma. Radiotherapy regimens after BCS were either a 5-week schedule with 5 weekly fractions of 5,7 Gy or a one-week schedule with 5 daily fractions of 5,2 Gy. Adverse events were recorded and local-relapse free survival (LRFS), locoregional-relapse free survival (LRRFS), metastasis-free survival (MFS), for breast-cancer specific survival (BCSS) and overall survival (OS) were evaluated. RESULTS: Between December 2014 and December 2022, 396 patients (400 breasts) were treated with ultrahypofractionated radiotherapy. Five-year LRFS was 98.8% (95% confidence interval: 97.1%-100%), and 5-year OS was 96.0% (95%CI: 92.6-99.5%). Age was statistically associated with OS in univariate analysis (HR: 1.16, 95%CI: 1.04-1.42, p = .01). Four patients (1.0%) experienced acute grade 3 radiation-induced adverse events, and 8 patients (2.3%) acute grade 2 toxicities. Twenty-three patients (5.8%) experienced late toxicity, all of them being graded as grade 1. The use of the 5.7 Gy-weekly-fraction regimen and the delivery of a tumor bed boost were significantly associated with acute radiodermatitis (p < .01; p = .02; respectively) and late fibrosis (p < .01; p = .049; respectively). CONCLUSIONS: ultrahypofractionated radiotherapy was associated with an excellent tumor control rate in our 'real-life' cohort with low-risk breast cancer patients. However, delivery of a tumor bed boost and using weekly 5.7-Gy fractions were associated with an increased risk of acute and late cutaneous toxicities.

Medial meniscal repair in stable knees: Survival rate and risk factors for failure at a minimum of 5 years.

INTRODUCTION: The menisci play a major role in the protection of the knee against osteoarthritis. A medial meniscus (MM) tear occurring in a stable knee is more at risk of repair failure than a suture concomitant with reconstruction of the anterior cruciate ligament. HYPOTHESIS: The survival of MM sutures in stable knees depends on the type of lesion. MATERIALS AND METHODS: This retrospective study was carried out as part of the 2022 Francophone Arthroscopy Society's symposium, across 10 centers (Bordeaux-Mérignac, Caen, Lille, Lille Louvière, Lyon, Marseille, Toulouse, Saint-Étienne, Strasbourg and Versailles) including medial meniscus sutures in stable knees performed before the end of 2017 (minimum 5 years of follow-up) with a collection of demographic, imaging, suture and postoperative protocol data, and a functional evaluation using the Knee injury and Osteoarthritis Outcome score (KOOS). The aim of this study was to analyze the medial meniscus sutures in stable knees and to evaluate their survival and their risk factors for failure according to the type of lesion; failure being defined by the use of a meniscectomy. RESULTS: Three-hundred and sixty-seven MM sutures, including 122 bucket-handle tears, were included. The KOOS score was improved by the meniscal suture by an average of 22.2 points for each sub-score (p<0.05), with an improvement, which was more marked for the bucket-handle tears. The failure rate, defined by revision surgery by meniscectomy, was 33% on average (42% for bucket-handles tears, 26% for others). The probability of survival was reduced for bucket-handle tears (62% at 5 years versus 77% for the other types). For all lesions, the main risk factor identified for failure was immediate weight-bearing [OR=3.6 (1.62; 7.98), p=0.0016]. Smoking was a failure risk factor for bucket-handle tears [OR=5.76 (1.81; 18.35), p=0.003]. CONCLUSION: MM sutures in stable knees improve knee function but present a different risk of failure depending on the type of lesion treated with a higher risk of failure for bucket-handle tears with the need for caution to be applied with regards to weight-bearing and smoking. LEVEL OF EVIDENCE: IV; retrospective series.

Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP) in patients with acute exacerbation of COPD: From the French OUTCOMEREA cohort.

BACKGROUND: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. METHODS: Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. RESULTS: Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01). CONCLUSION: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD.

The frequency of medial meniscal repairs in stable knees during one year of arthroscopic activity (2021-2022) - comparison with a retrospective study (prior to 2017).

INTRODUCTION: There has been a significant increase in the use of conservative treatment for meniscal lesions due to raised awareness around the need for meniscal preservation. However, sutures of the medial meniscus (MM) in stable knees remain less frequently used. The objective of this study was to, firstly, identify the MM suture rate over one year of activity; secondly, to identify and compare the distribution of MM sutures in stable, and stabilized, knees on this prospective series; and thirdly, to compare the evolution of practices with a retrospective series of more than 5 years follow-up. HYPOTHESIS: The number of MM sutures in stable knees represents a small percentage of annual arthroscopic activity. MATERIAL AND METHODS: This multicenter study was carried out in 10 reference centers participating in the 2022 symposium of the Francophone Society of Arthroscopy (Bordeaux, Caen, Lille, Lille Louvière, Lyon, Marseille, Toulouse, Saint-Étienne, Strasbourg, Versailles). This study included a prospective series on interventions performed under arthroscopy during one year of activity. The inclusion criteria were patients operated on via an arthroscopic technique and aged over 18 at the time of the operation. Demographic data, as well as the circumstances leading to the injury, were collected. A register of the lesions found was established in order to list the lesions of the MM, the lateral meniscus (LM), the anterior cruciate ligament (ACL), the associated chondral lesions; as well as the treatment performed: meniscal suture of the MM and/or LM, meniscectomy of the MM and/or LM and ligamentoplasty of the ACL. This study also included a retrospective series comprised of only MM sutures in stable knees at more than 5 years of follow-up. RESULTS: Of the 4154 patients included, 1919 patients (46.2%) underwent surgery for ACL reconstruction and 2235 for arthroscopy without associated ligament surgery. MM sutures (in stable knees and in knees with ACL reconstruction) represented 14% of the overall arthroscopic activity (583 MM sutures) versus 8.6% for LM (360 sutures). In cases of ACL surgery, there were 895 associated meniscal lesions (337 LM and 558 MM) and 66% of MM tears (371 MM sutures) were sutured. In stable knees, MM tears were weaker (212 MM sutures out of 1359 lesions, i.e. 15%). Of all the arthroscopic procedures performed over the course of a year, MM suturing in stable knees represented 5.1% of the activity. Compared to the retrospective series (n=367), the patients were older (37 years versus 28 years) and the management of ramp lesions or root tears was noted. In both series, these tears were related to sports trauma in more than 70% of cases. CONCLUSION: MM suturing in stable knees represents a small part of annual arthroscopic activity and it occurs less frequently than during ACL reconstruction surgery. LEVEL OF EVIDENCE: IV.

The impact of methane leakage on the role of natural gas in the European energy transition.

Decarbonising energy systems is a prevalent topic in the current literature on climate change mitigation, but the additional climate burden caused by methane emissions along the natural gas value chain is rarely discussed at the system level. Considering a two-basket greenhouse gas neutrality objective (both CO2 and methane), we model cost-optimal European energy transition pathways towards 2050. Our analysis shows that adoption of best available methane abatement technologies can entail an 80% reduction in methane leakage, limiting the additional environmental burden to 8% of direct CO2 emissions (vs. 35% today). We show that, while renewable energy sources are key drivers of climate neutrality, the role of natural gas strongly depends on actions to abate both associated CO2 and methane emissions. Moreover, clean hydrogen (produced mainly from renewables) can replace natural gas in a substantial proportion of its end-uses, satisfying nearly a quarter of final energy demand in a climate-neutral Europe.

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. MATERIALS AND METHODS: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. RESULTS: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. CONCLUSION: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Multicentre medicoeconomic evaluation of cardiac magnetic resonance imaging for predicting coronary artery disease in left ventricular dysfunction: The CAMAREC study design.

BACKGROUND: Cardiac magnetic resonance imaging may provide a non-invasive alternative to coronary angiography for differentiating between ischaemic and non-ischaemic cardiomyopathy in cases of unexplained reduced left ventricular ejection fraction. AIM: The CAMAREC study aims to evaluate the diagnostic accuracy of cardiac magnetic resonance imaging in predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, using coronary angiography as the gold standard for comparison. METHODS: CAMAREC is a prospective cohort study of 406 patients in 10 centres with newly diagnosed, unexplained left ventricular ejection fraction ≤ 45%. Cardiac magnetic resonance imaging and coronary angiography will be conducted within a 2-week interval, starting with cardiac magnetic resonance imaging; independent committees will review the results blindly. Primary outcome is sensitivity of detecting ischaemic scar on cardiac magnetic resonance imaging for predicting significant coronary artery disease on coronary angiography according to Felker's criteria. Secondary outcomes include specificity and positive and negative predictive values (with 95% confidence intervals) of cardiac magnetic resonance imaging for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, kappa concordance coefficient between cardiac magnetic resonance imaging and coronary angiography for diagnosing the affected myocardial territory, and the impact of cardiac magnetic resonance imaging on revascularization decisions. Two ancillary studies will evaluate the incremental cost-effectiveness of using cardiac magnetic resonance imaging first versus coronary angiography first, and the sensitivity of pre- and postcontrast T1-mapping for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction. CONCLUSION: Our study protocol is designed to rigorously evaluate cardiac magnetic resonance imaging as a non-invasive alternative to coronary angiography in patients with unexplained reduced left ventricular ejection fraction. The results will have significant implications for patient management, and may support growing evidence for the clinical utility of cardiac magnetic resonance imaging.

Ancient dolphin genomes reveal rapid repeated adaptation to coastal waters.

Parallel evolution provides strong evidence of adaptation by natural selection due to local environmental variation. Yet, the chronology, and mode of the process of parallel evolution remains debated. Here, we harness the temporal resolution of paleogenomics to address these long-standing questions, by comparing genomes originating from the mid-Holocene (8610-5626 years before present, BP) to contemporary pairs of coastal-pelagic ecotypes of bottlenose dolphin. We find that the affinity of ancient samples to coastal populations increases as the age of the samples decreases. We assess the youngest genome (5626 years BP) at sites previously inferred to be under parallel selection to coastal habitats and find it contained coastal-associated genotypes. Thus, coastal-associated variants rose to detectable frequencies close to the emergence of coastal habitat. Admixture graph analyses reveal a reticulate evolutionary history between pelagic and coastal populations, sharing standing genetic variation that facilitated rapid adaptation to newly emerged coastal habitats.

Multiple Myeloma Spinal Lesion Care: Management of a Primary Bone Malignancy Rather Than a Spinal Metastasis.

OBJECTIVE: Multiple myeloma (MM) is too often wrongly categorized as a spinal metastasis (SpM), although it is distinguishable from SpM in many aspects, such as its earlier natural history at the time of diagnosis, its increased overall survival (OS), and its response to therapeutic modalities. The characterization of these 2 different spine lesions remains a main challenge. METHODS: This study compares 2 consecutive prospective oncologic populations of patients with spine lesions: 361 patients treated for MM spine lesions and 660 patients treated for SpM between January 2014 and 2017. RESULTS: The mean time between the tumor/MM diagnosis and spine lesions was respectively 0.3 (standard deviation [SD] 4.1) and 35.1 months (SD 21.2) for the MM and SpM groups. The median OS for the MM group was 59.6 months (SD 6.0) versus 13.5 months (SD 1.3) for the SpM group (P < 0.0001). Regardless of Eastern Cooperative Oncology Group (ECOG) performance status, patients with MM always have a significantly better median OS than do patients with SpM: ECOG 0, 75.3 versus 38.7 months; ECOG 1, 74.3 versus 24.7 months; ECOG 2, 34.6 versus 8.1 months; ECOG 3, 13.5 versus 3.2 months and ECOG 4, 7.3 versus 1.3 months (P < 0.0001). The patients with MM had more diffuse spinal involvement (mean, 7.8 lesions; SD 4.7) than did patients with SpM (mean, 3.9; SD 3.5) (P < 0.0001). CONCLUSIONS: MM must be considered as a primary bone tumor, not as SpM. The strategic position of the spine in the natural course of cancer (i.e., nurturing cradle of birth for MM vs. systemic metastases spreading for SpM) explains the differences in OS and outcome.