Using technology to improve reconnection to remote monitoring in cardiac implantable electronic device patients.

Background: Remote monitoring (RM) of cardiac implantable electronic device (CIED) patients is now considered standard of care. However, a fundamental requirement of RM is continuous connectivity between the patient's implanted device and the CIED manufacturer's central server. This study examined the rate of RM disconnections in CIED recipients and the impact of short message service (SMS) to facilitate reconnections. Methods: Using a platform that collects RM data from CIED manufacturers, we retrospectively examined the disconnection and reconnection events in 6085 patients from 20 medical centers. Each medical center reported their usual practice regarding RM disconnections, which consisted of either an automatic SMS from the platform to patients who were disconnected for 2 weeks or the standard of care (SC) of a phone call to patients. Results: During a 1-year period, 43% of patients had at least 1 disconnection. Half of these patients experienced multiple disconnections. The use of SMS reduced the time to reconnection by 43% in comparison to SC. The median time to reconnect a disconnected patient was 11.0 [3.2, 29.0] days for SC vs 6.3 [1.3, 22.0] days for SMS (P < .0001). Furthermore, there was a high rate of reconnections within the first 48 hours of the SMS message, which was nearly double that in the SC arm. Conclusion: This study demonstrates the feasibility of an automatic system to deliver an SMS to patients with a disconnected CIED to facilitate early reconnection to RM.

Mpox outbreak in France: epidemiological characteristics and sexual behaviour of cases aged 15 years or older, 2022.

BackgroundLocally-acquired mpox cases were rarely reported outside Africa until May 2022, when locally-acquired-mpox cases occurred in various European countries.AimWe describe the mpox epidemic in France, including demographic and behavioural changes among a subset of cases, during its course.MethodsData were retrieved from the enhanced national surveillance system until 30 September 2022. Laboratory-confirmed cases tested positive for monkeypox virus or orthopoxviruses by PCR; non-laboratory-confirmed cases had clinical symptoms and an epidemiological link to a laboratory-confirmed case. A subset of ≥ 15-year-old male cases, notified until 1 August, was interviewed for epidemiological, clinical and sexual behaviour information. Association of symptom-onset month with quantitative outcomes was evaluated by t- or Wilcoxon tests, and with binary outcomes, by Pearson's chi-squared or Fisher exact tests.ResultsA total of 4,856 mpox cases were notified, mostly in Île-de-France region (62%; 3,025/4,855). Cases aged ≥ 15 years were predominantly male (97%; 4,668/4,812), with 37 years (range: 15-81) as mean age. Between May and July, among the subset interviewed, mpox cases increased in regions other than Île-de-France, and mean age rose from 35 (range: 21-64) to 38 years (range: 16-75; p = 0.007). Proportions of cases attending men-who-have-sex-with-men (MSM) meeting venues declined from 60% (55/91) to 46% (164/359; p = 0.012); median number of sexual partners decreased from four (interquartile range (IQR): 1-10) to two (IQR: 1-4; p < 0.001).ConclusionChanges in cases' characteristics during the epidemic, could reflect virus spread from people who were more to less behaviourally vulnerable to mpox between May and July, or MSM reducing numbers of sexual partners as recommended.

An Automated Surveillance System (SurCeGGID) for the French Sexually Transmitted Infection Clinics: Epidemiological Monitoring Study.

BACKGROUND: Viral and bacterial sexually transmitted infections (STIs) are public health concerns worldwide, but surveillance systems are not comprehensive enough to design and monitor accurately STI control strategies in most countries. In 2016, 320 STI clinics (CeGIDDs in French) were implemented in France, primarily targeting most exposed populations, although access is free of charge for anybody. OBJECTIVE: This article describes the mandatory surveillance system (SurCeGIDD) based on CeGIDD's individual data aiming to better guide STI prevention. METHODS: A decree ensured the use of software to manage consultations in CeGIDDs and to transfer surveillance data. A web service was implemented to secure data transfer from CeGIDDs' software to a centralized database. CeGIDDs can also transfer data in CSV format via a secured data-sharing platform. Then, data are automatically checked before integration. Data on sociodemographic variables, sexual exposure, blood exposure, symptoms, STI tests, STI diagnoses, and sexual health services delivery were collected for the previous year (n-1). Preliminary and descriptive analyses of 2017-2018 data transmitted in 2018 and 2019, respectively, were performed using numbers and proportions for qualitative variables. RESULTS: In 2017, 54/320 (16.9%) CeGIDDs transmitted their data. In 2018, this number of participants increased to 143/320 (44.7%) CeGIDDs. The corresponding volume of records increased from 2414 in 2017 to 382,890 in 2018. In 2018, most attendances were hospital based (263,480/382,890, 68.81%). In 2018, attendees were mostly men 227,326/379,921 (59.84%), while 151,963/379,921 (40%) were women 632/379,921 (0.17%) transgenders. The median age was 27 years for men, 23 years for women, and 30 years for transgender. Half of the attendees (81,964/174,932, 46.85%) were heterosexual men, 69,016/174,932 (39.45%) heterosexual women, 20,764/174,932 (11.87%) men who have sex with men, and 3188/174,932 (1.82%) women who have sex with women. A majority of them were born in France (227,698/286,289, 79.53%) and unemployed 115,913/211,707 (54.75%). The positivity rates were 0.37% for 205,348 HIV serologies, 1.31% for 131,551 hepatitis B virus serologies, 7.16% for 161,241 Chlamydia trachomatis PCR, 2.83% for 146,649 gonorrhea PCR, 1.04% for the syphilis combination of treponema and nontreponema serologies, and 5.96% for 13,313 Mycoplasma genitalium PCR. CONCLUSIONS: Despite challenges, the effectiveness of the SurCeGIDD surveillance based on routine patients' records was demonstrated. The wide range of information, including socioeconomic determinants, might help to better guide and evaluate the prevention policies and services delivery. However, the growing volumes of information will require adapted tools and algorithms for the data management and analyses.

Impact of the Omicron variant on SARS-CoV-2 reinfections in France, March 2021 to February 2022.

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.

Discovery and Biotechnological Exploitation of Glycoside-Phosphorylases.

Among carbohydrate active enzymes, glycoside phosphorylases (GPs) are valuable catalysts for white biotechnologies, due to their exquisite capacity to efficiently re-modulate oligo- and poly-saccharides, without the need for costly activated sugars as substrates. The reversibility of the phosphorolysis reaction, indeed, makes them attractive tools for glycodiversification. However, discovery of new GP functions is hindered by the difficulty in identifying them in sequence databases, and, rather, relies on extensive and tedious biochemical characterization studies. Nevertheless, recent advances in automated tools have led to major improvements in GP mining, activity predictions, and functional screening. Implementation of GPs into innovative in vitro and in cellulo bioproduction strategies has also made substantial advances. Herein, we propose to discuss the latest developments in the strategies employed to efficiently discover GPs and make the best use of their exceptional catalytic properties for glycoside bioproduction.

Assessing the management of major bleeding events in patients treated by direct oral anticoagulant in an emergency department.

Since direct oral anticoagulants have been marketed, the management of major bleeding in emergency departments has become more challenging. In 2013 and 2016, the Working Group in Perioperative Haemostasis made several proposals for this. The objective of the present study was to evaluate conformity with these proposals in daily clinical practice. We performed a retrospective single-center cohort study addressing the management of major bleeding in patients treated by direct oral anticoagulant in an emergency department. Patients were included between January 1, 2015 and November 30, 2017. Among 3,365 patients admitted to the emergency department for bleeding, a total of 191 were treated by direct oral anticoagulant and 55 (28.8%) with major bleeding were included in the present study. The majority of patients received rivaroxaban (n = 44, 80.0%) and were treated for atrial fibrillation (n = 47, 85.0%). Bleeding concerned gastrointestinal (n = 30, 54.6%) and (n = 14, 25.5%) intracranial location. Twenty-one patients (38.2%) were treated by prothrombin complex concentrate, and 31 patients (56.4%) were transfused. Intervention for hemostatic control was performed for 30 patients (54.6%). Thirty-three patients (60.0%) presented a deviation from protocol. There is no significant difference for mortality at 3 months according to whether or not there was a deviation from protocol. Nearly two-thirds of patients with major bleeding associated with direct oral anticoagulant administration had protocol deviation, but there was no effect on mortality.

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases.

Generally, carbohydrate-active enzymes are studied using chromogenic substrates that provide quick and easy color-based detection of enzyme-mediated hydrolysis. For feruloyl esterases, commercially available chromogenic ferulate derivatives are both costly and limited in terms of their experimental application. In this study, we describe solutions for these two issues, using a chemoenzymatic approach to synthesize different ferulate compounds. The overall synthetic routes towards commercially available 5-bromo-4-chloro-3-indolyl and 4-nitrophenyl 5-O-feruloyl-α-ʟ-arabinofuranosides were significantly shortened (from 7 or 8 to 4-6 steps), and the transesterification yields were enhanced (from 46 to 73% and from 47 to 86%, respectively). This was achieved using enzymatic (immobilized Lipozyme® TL IM from Thermomyces lanuginosus) transesterification of unprotected vinyl ferulate to the primary hydroxy group of α-ʟ-arabinofuranosides. Moreover, a novel feruloylated 4-nitrocatechol-1-yl-substituted butanetriol analog, containing a cleavable hydroxylated linker, was also synthesized in 32% overall yield in 3 steps (convergent synthesis). The latter route combined the regioselective functionalization of 4-nitrocatechol and enzymatic transferuloylation. The use of this strategy to characterize type A feruloyl esterase from Aspergillus niger reveals the advantages of this substrate for the characterizations of feruloyl esterases.

Anomeric Retention of Carbohydrates in Multistage Cyclic Ion Mobility (IMSn): De Novo Structural Elucidation of Enzymatically Produced Mannosides.

Carbohydrates are complex structures that still challenge analysts today because of their different levels of isomerism, notably the anomerism of the glycosidic bond. It has been shown recently that anomerism is preserved upon gas-phase fragmentation and that high-resolution ion mobility (IMS) can distinguish anomers. However, these concepts have yet to be applied to complex biological products. We have used high-resolution IMS on a cyclic device to characterize the reaction products of Uhgb_MS, a novel mannoside synthase of the GH130 family. We designed a so-called IMSn sequence consisting of (i) separating and isolating specific IMS peaks, (ii) ejecting ions to a pre-array store cell depending on their arrival time, (iii) inducing collisional activation upon reinjection, and (iv) performing multistage IMS analysis of the fragments. First, we applied IMS2 sequences to purely linked α1,2- and ß1,2-mannooligosaccharides, which provided us with reference drift times for fragments of known conformation. Then, we performed IMSn analyses of enzymatically produced mannosides and, by comparison with the references, we succeeded in determining the intrachain anomerism of a α1,2-mannotriose and a mix-linked ß/α1,2-mannotetraose-a first for a crude biological medium. Our results show that the anomerism of glycosides is maintained through multiple stages of collisional fragmentation, and that standalone high-resolution IMS and IMSn can be used to characterize the intrachain anomerism in tri- and tetrasaccharides in a biological medium. This is also the first evidence that a single carbohydrate-active enzyme can synthesize both α- and ß-glycosidic linkages.

French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long.

BACKGROUND: Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). METHODS: The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. RESULTS: Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). CONCLUSIONS: This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

Analysis of the diversity of the glycoside hydrolase family 130 in mammal gut microbiomes reveals a novel mannoside-phosphorylase function.

Mannoside phosphorylases are involved in the intracellular metabolization of mannooligosaccharides, and are also useful enzymes for the in vitro synthesis of oligosaccharides. They are found in glycoside hydrolase family GH130. Here we report on an analysis of 6308 GH130 sequences, including 4714 from the human, bovine, porcine and murine microbiomes. Using sequence similarity networks, we divided the diversity of sequences into 15 mostly isofunctional meta-nodes; of these, 9 contained no experimentally characterized member. By examining the multiple sequence alignments in each meta-node, we predicted the determinants of the phosphorolytic mechanism and linkage specificity. We thus hypothesized that eight uncharacterized meta-nodes would be phosphorylases. These sequences are characterized by the absence of signal peptides and of the catalytic base. Those sequences with the conserved E/K, E/R and Y/R pairs of residues involved in substrate binding would target ß-1,2-, ß-1,3- and ß-1,4-linked mannosyl residues, respectively. These predictions were tested by characterizing members of three of the uncharacterized meta-nodes from gut bacteria. We discovered the first known ß-1,4-mannosyl-glucuronic acid phosphorylase, which targets a motif of the Shigella lipopolysaccharide O-antigen. This work uncovers a reliable strategy for the discovery of novel mannoside-phosphorylases, reveals possible interactions between gut bacteria, and identifies a biotechnological tool for the synthesis of antigenic oligosaccharides.

Epidemiology of Clostridioides difficile infections, France, 2010 to 2017.

BackgroundClostridioides difficile is a leading cause of healthcare-associated diarrhoea in middle and high-income countries. Up to 2018, there has been no systematic, annual surveillance for C. difficile infections (CDI) in France.AimsTo provide an updated overview of the epidemiology of CDI in France between 2010 and 2017 based on five different data sources.MethodsThis is a descriptive study of retrospective surveillance and alerts data. Incidence of CDI cases was estimated through the CDI incidence survey (2016) and data from the French National Uniform Hospital Discharge Database (PMSI; 2010-16). Testing frequency for CDI was estimated through the CDI incidence survey and point prevalence studies on healthcare-associated infections (HAI; 2012 and 2017). The national early warning response system for HAI (HAI-EWRS, 2012-17) and National Reference Laboratory data (2012-17) were used to follow the number of severe CDI cases and/or outbreaks.ResultsIn 2016, CDI incidence in acute care was 3.6 cases per 10,000 patient days (PD). There was a statistically significant increase in CDI incidence between 2010 and 2016 (+ 14% annually) and testing frequency was 47.4 per 10,000 PD. The number of CDI HAI-EWRS notifications decreased between 2015 and 2017 with only a few large outbreaks reported.ConclusionThe CDI incidence estimate increased from 2010, but remained below the European average of 7 per 10,000 PD in 2014; there were fewer severe cases or clusters reported in France. The consistency between PMSI and laboratory-based estimated CDI incidence could allow for more routine monitoring of CDI incidence.

Rapid and large-scale implementation of HCV treatment advances in France, 2007-2015.

BACKGROUND: The last decade was marked by major advances in HCV treatment with the introduction of first wave protease inhibitors (1st-wave PIs, telaprevir or boceprevir) in 2011 and second direct-acting antivirals (2nd-wave DAAs) in 2014, that followed low effective pegylated interferon α / ribavirin bitherapy. We estimated the number of patients initiating HCV treatment in France between 2007 and 2015 according to the type of therapy, described their demographical characteristics, and estimated how many were cured with 2nd-wave DAAs in 2014-2015. METHODS: Individual data from the national health insurance information system were analysed. HCV treatment initiation was defined as a drug reimbursement in the absence of any reimbursement for the same drug in the previous six weeks. RESULTS: Between 2007 and 2015, 72,277 patients initiated at least one HCV treatment. The annual number of patients initiating treatment decreased from 2007 (~13,300) to 2010 (~10,000). It then increased with the introduction of 1st-wave PIs (~12,500 in 2012), before decreasing again in 2013 (~8400). A marked increase followed upon the approval of 2nd-wave DAAs in 2014 (~11,600). Approximately, 8700 and 14,700 patients initiated 2nd-wave DAAs in 2014 and 2015, respectively, corresponding to an estimated 20,300 cured patients in 2014-2015. Patients initiating HCV treatment were mostly male (~65% throughout the 9-year period). Women were older than men (mean age: 55.0 vs. 48.9). Increasing age was associated with more advanced treatment. Among patients initiating 2nd-wave DAAs, the proportions of those under 40 and over 79 years old increased between 2014 and 2015, whereas the proportion of those previously treated for HCV 2007 onwards declined. CONCLUSIONS: Successive advances in HCV treatment have been rapidly and widely implemented in France. With the announcement of universal access to DAAs in mid-2016 and price reductions, access to 2nd-wave DAAs is expected to expand even more.

Genetic aspects of adrenocortical tumours and hyperplasias.

Adrenocortical tumours (ACT), which include adenomas, carcinomas and adrenal hyperplasia, may be associated with genetic syndromes, such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1, familial adenomatous polyposis and Carney complex. Genetic defects have been found to be responsible for the disease in most of these syndromes, allowing genetic counselling to affected patients and family members. Here, we summarize the clinical criteria of these hereditary syndromes and briefly describe the genetic alterations related to them. In addition, we discuss the involvement of various genetic defects in the development of sporadic adrenocortical tumours.

Identification of genetic alterations of AXIN2 gene in adrenocortical tumors.

BACKGROUND: Mutations of the ß-catenin gene (CTNNB1), which lead to constitutive activation of Wnt signaling, have recently been described in adrenocortical adenomas (AA) and carcinomas (ACC). However, somatic CTNNB1 mutations may explain only about 50% of ß-catenin accumulation observed in adrenocortical tumors, indicating that other components of the Wnt pathway may be involved. OBJECTIVE: The objective of the study was to investigate whether alterations in AXIN2 may be present in adrenocortical tumors. METHODS: We studied 49 human adrenocortical samples: 30 AA, six ACC, five primary pigmented nodular adrenocortical disease five ACTH-independent macronodular adrenal hyperplasias (AIMAH), and three ACTH-dependent hyperplasias in addition to the human ACC cell lines SW13 and H295R. Samples were screened for somatic genetic alterations in exon 3 of CTNNB1 and exons 5, 7, and 9 of AXIN2. RESULTS: We found an in-frame, 12-bp deletion beginning at coding nucleotide 2013 in exon 7 of the AXIN2 gene, c.2013_2024del12 (p.Arg671_Pro674del), in two of 30 AA (7%), one of six ACC (17%), and the ACC H295R cell line. Immunohistochemistry revealed that tumors with AXIN2 genetic defects showed nuclear/cytoplasmic accumulation of ß-catenin, indicating the activation of Wnt signaling. In addition, the ACC and H295R cells with AXIN2 deletion (c.2013_2024del12) harbored p.Ser45del and p.Ser45Pro CTNNB1 mutations, respectively. Two single-nucleotide polymorphisms were identified in exon 7 of AXIN2, c.2351C>T in 2 AA, and one AIMAH and c.2342A>G in an AIMAH tissue. CONCLUSION: The present study reports, for the first time, that AXIN2 genetic defects may be found in adrenocortical tumors. However, the functional consequence of this genetic alteration remains to be determined.

Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.

BACKGROUND: Mutations of ß-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and adrenocortical carcinomas (ACC). However, the target genes of ß-catenin have not yet been identified in adrenocortical tumors. OBJECTIVE: Our objective was to identify genes deregulated in adrenocortical tumors harboring CTNNB1 genetic alterations and nuclear accumulation of ß-catenin. METHODS: Microarray analysis identified a dataset of genes that were differently expressed between AA with CTNNB1 mutations and wild-type (WT) tumors. Within this dataset, the expression profiles of five genes were validated by real time-PCR (RT-PCR) in a cohort of 34 adrenocortical tissues (six AA and one ACC with CTNNB1 mutations, 13 AA and four ACC with WT CTNNB1, and 10 normal adrenal glands) and two human ACC cell lines. We then studied the effects of suppressing ß-catenin transcriptional activity with the T-cell factor/ß-catenin inhibitors PKF115-584 and PNU74654 on gene expression in H295R and SW13 cells. RESULTS: RT-PCR analysis confirmed the overexpression of ISM1, RALBP1, and PDE2A and the down-regulation of PHYHIP in five of six AA harboring CTNNB1 mutations compared with WT AA (n = 13) and normal adrenal glands (n = 10). RALBP1 and PDE2A overexpression was also confirmed at the protein level by Western blotting analysis in mutated tumors. ENC1 was specifically overexpressed in three of three AA harboring CTNNB1 point mutations. mRNA expression and protein levels of RALBP1, PDE2A, and ENC1 were decreased in a dose-dependent manner in H295R cells after treatment with PKF115-584 or PNU74654. CONCLUSION: This study identified candidate genes deregulated in CTNNB1-mutated adrenocortical tumors that may lead to a better understanding of the role of the Wnt-ß-catenin pathway in adrenocortical tumorigenesis.

Hypoparathyroidism in systemic lupus erythematosus.

Hypoparathyroidism is a rare disease. The main cause of hypoparathyroidism is postsurgical hypoparathyroidism. However, cases of hypoparathyroidism in patients suffering from SLE exist although it is uncommon. Only three previous cases have been reported. We present the case of a woman suffering both from systemic lupus erythematosus and hypoparathyroidism. This reported association of hypoparathyroidism with lupus expands the spectrum of endocrine disorders seen in this disease. We suggest that there may be a common underlying pathophysiological process linking these diseases.