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Rhodococcus equi is a rare human opportunistic pathogen that has been increasingly reported in recent decades. It mainly affects immunosuppressed patients, and in particular human immunodeficiency virus (HIV)–infected patients, where it typically presents as cavitary pneumonia. Early treatment with combined and effective antimicrobials and antiretroviral therapy after prompt diagnosis is essential to ensure an optimal outcome. We present a case series of three human Rhodococcus equi infections in HIV‐infected patients with advanced immune suppression, treated at the University Hospital of Antwerp, Belgium. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the timeliness of rabies post-exposure prophylaxis (PEP) and the proportion of individuals with an adequate antibody response post-PEP among those attending the Belgian national reference center., Methods: Retrospective analysis of patient records who attended our center from 2018 to 2023. Delay was defined as rabies immunoglobulin (RIG) and vaccine initiation beyond 2 calendar days after exposure. Antibodies were measured by rapid fluorescent focus inhibition test (RFFIT) after PEP in high-risk exposures. A titer ≥0.5 IU/ml was considered adequate., Results: We reviewed 317 patient records. Among individuals with inland exposure (n = 103), 85 % timely received PEP. Among travelers exposed abroad (n = 214), administration of RIG and vaccine initiation were timely in 30 % and 50 % of cases, respectively. An adequate antibody response was detected in 99.5 % (195/196) individuals., Conclusion: Substantial PEP delays among travelers were observed. The robust antibody responses suggest that routine serological follow-up is not necessary for all patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial resistance (AMR) is a global problem that results in high morbidity and mortality, particularly in low- and middle-income countries. Inappropriate use of antimicrobials is a major driver of AMR. This study aimed to evaluate the rate and quality of antimicrobial prescription and use at the University Teaching Hospital of Kigali (CHUK), a tertiary-referral teaching hospital. Methodology: A point prevalence survey (PPS) of antimicrobial prescription was conducted using the Global PPS tool, including a healthcare-acquired infection (HAI) module. Results: On the day of the PPS, 39.3% (145/369) of inpatients were prescribed at least one antimicrobial. Out of the 259 prescribed antimicrobials, 232 (89.6%) were antibacterials, of which 151 (65.1%) belonged to the watch group of the WHO AWaRe classification. The top three antibiotics prescribed were cefotaxime (87; 37.5%), parenteral metronidazole (31; 13.4%), and meropenem (23; 9.9%). Stop or review dates for the prescribed antimicrobials were documented in 27/259 prescriptions (10.4%). Surgical prophylaxis (SP) was prescribed for longer than one day in 83.3% of 61 patients. Samples for culture were sent for 27.1% (63/232) of all the patients prescribed antibiotics. Conclusion: This PPS demonstrates multiple indicators of the poor use of antimicrobials, including the high prevalence usage of watch antibiotics and prolonged surgical prophylaxis and other poor-quality indicators. Thus, there is an urgent need for intervention to improve antimicrobial stewardship.

Background: Antimicrobial resistance (AMR) is a global health crisis, with Enterobacterales including Escherichia coli and Klebsiella pneumoniae playing significant roles. While international travel to low- and middle-income countries is linked to colonisation with AMR Enterobacterales, the clinical implications, particularly the risk of subsequent infection, remain unclear due to limited data. We aimed to characterise E. coli and K. pneumoniae infections in travellers and the antimicrobial susceptibility profiles of their isolates., Methods: We analysed data on E. coli and K. pneumoniae infections in travellers collected at GeoSentinel sites between 2015 and 2022, focusing on epidemiological, clinical and microbiological characteristics. We defined multi-drug resistance (MDR) as non-susceptibility to agents from at least three drug classes., Results: Over the 8-year period, we included 655 patients (median age 41 years; 74% female) from 57 sites in 27 countries, with 584 E. coli and 72 K. pneumoniae infections. Common travel regions included Sub-Saharan Africa, Southeast Asia, and South-Central Asia. Urinary tract infections predominated. Almost half (45%) were hospitalised. Among infections with antimicrobial susceptibility data across three or more drug classes, 203/544 (37%) E. coli and 19/67 (28%) K. pneumoniae demonstrated MDR. Over one-third of E. coli and K. pneumoniae isolates were non-susceptible to third-generation cephalosporins and cotrimoxazole, with 38% and 28% non-susceptible to fluoroquinolones, respectively. Travellers to South-Central Asia most frequently had isolates non-susceptible to third-generation cephalosporins, fluoroquinolones and carbapenems. We observed increasing frequencies of phenotypic extended spectrum beta-lactamase and carbapenem resistance over time., Conclusions: E. coli and K. pneumoniae infections in travellers, particularly those to Asia, may be challenging to empirically treat. Our analysis highlights the significant health risks these infections pose to travellers and emphasises the escalating global threat of AMR. Enhanced, systematic AMR surveillance in travellers is needed, along with prospective data on infection risk post travel-related AMR organism acquisition., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society of Travel Medicine.)

Purpose: Few studies have compared patient characteristics, clinical management, and outcome of patients with COVID-19 between the different epidemic waves. In this study, we describe patient characteristics, treatment, and outcome of patients admitted for COVID-19 in the Antwerp University Hospital over the first three epidemic waves of 2020-2021., Methods: Retrospective observational study of COVID-19 patients in a Belgian tertiary referral hospital. All adult patients with COVID-19, hospitalized between February 29, 2020, and June 30, 2021, were included. Standardized routine medical data was collected from patient records. Risk factors were assessed with multivariable logistic regression., Results: We included 722 patients, during the first (n = 179), second (n = 347) and third (n = 194) wave. We observed the lowest disease severity at admission during the first wave, and more elderly and comorbid patients during the second wave. Throughout the subsequent waves we observed an increasing use of corticosteroids and high-flow oxygen therapy. In spite of increasing number of complications throughout the subsequent waves, mortality decreased each wave (16.6%,15.6% 11.9% in 1st, 2nd and 3rd wave respectively). C-reactive protein above 150 mg/L was predictive for the need for intensive care unit admission (odds ratio (OR) 3.77, 95% confidence interval (CI) 2.32-6.15). A Charlson comorbidity index ≥ 5 (OR 5.68, 95% CI 2.54-12.70) and interhospital transfers (OR 3.78, 95% CI 2.05-6.98) were associated with a higher mortality., Conclusions: We observed a reduction in mortality each wave, despite increasing comorbidity. Evolutions in patient management such as high-flow oxygen therapy on regular wards and corticosteroid use may explain this favorable evolution., (© 2024. The Author(s).)

An efficient copper-catalyzed synthesis of (annelated) benzimidazoles is reported. This transformation is based on a simple and straightforward one-pot sequence involving a copper-catalyzed cross coupling between o -haloanilines and lactams/amides followed by a subsequent cyclization under acidic conditions. A variety of (annelated) benzimidazoles could be easily obtained in high yields from readily available starting materials, and this procedure could be further applied to the synthesis of the antihypertensive blockbuster drug telmisartan.

T-cell-based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3β TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2-associated CDR3α and CDR3β sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2-associated CDR3α/β sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic area under the curve of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historical exposure. In essence, this work presents a new paradigm for applying the T-cell repertoire to accomplish TCR-based diagnostics., Competing Interests: Potential conflicts of interest . B. O., K. L., and P. M. are cofounders, board directors, and shareholders of ImmuneWatch. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to SARS-CoV-2 epitopes unique to the virus (SC2-unique) or shared with other coronaviruses (CoV-common), we trained a large number of T-cell receptor (TCR) - epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. These models were then applied to longitudinal CD8+ TCR repertoires from critical and non-critical COVID-19 patients. In spite of comparable initial CoV-common TCR repertoire depth and CD8+ T-cell depletion, the temporal dynamics of SC2-unique TCRs differed depending on the disease severity. Specifically, while non-critical patients demonstrated a large and diverse SC2-unique TCR repertoire by the second week of the disease, critical patients did not. Furthermore, only non-critical patients exhibited redundancy in the CD8+ T-cell response to both groups of epitopes, SC2-unique and CoV-common. These findings indicate a valuable contribution of the SC2-unique CD8+ TCR repertoires. Therefore, a combination of specific and cross-reactive CD8+ T-cell responses may offer a stronger clinical advantage. Besides tracking the specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire, our analytical framework can be expanded to more epitopes and assist in the assessment and monitoring of CD8+ T-cell response to other infections., Competing Interests: BO, KL, and PM are co-founders, board directors and shareholders of ImmuneWatch™. None of the work presented here was influenced in any way by this. ImmuneWatch™ had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Postovskaya, Vujkovic, de Block, van Petersen, van Frankenhuijsen, Brosius, Bottieau, Van Dijck, Theunissen, van Ierssel, Vlieghe, Bartholomeus, Mullan, Adriaensen, Vanham, Ogunjimi, Laukens, Vercauteren and Meysman.)

Ammonium salts are usually considered as highly challenging to reduce into the corresponding radicals because of the strength of their carbon-nitrogen bond. Here, we disclose that several ammonium salts can be readily activated using iridium photoredox catalysis to form radicals and illustrate the synthetic utility of this activation of strong C-N bonds with hydrodeamination reactions and radical couplings. Cyclic voltammetry was exploited to rationalize the reactivity observed for the activation of these ammonium salts.

Background: Information on human filariasis in international travelers is scarce. We describe the epidemiology, clinical presentation, and outcome of these infections in a reference travel clinic over the past decades., Methods: We reviewed all cases of filariasis diagnosed at the Institute of Tropical Medicine, Antwerp, Belgium, from 1994 to 2018. Diagnosis was obtained by either parasitological methods (confirmed) or strict clinical case definitions (probable). We assessed the characteristics of cases at diagnosis and response to therapy within 3-12 months., Results: A total of 320 patients (median age: 41 years; 71% males) were diagnosed with 327 filarial infections (Wuchereria bancrofti = 6, Onchocerca volvulus = 33, Loa loa = 150, Mansonella perstans = 130, unspecified species = 8). Diagnosis was confirmed in 213/320 (67%) patients. European long-term travelers accounted for 166 patients (52%) and visitors/migrants from tropical countries for another 110 (34%). Central Africa was the likely region of acquisition for 294 (92%) patients. The number of filariasis cases decreased from 21.5/year on average in the 1990s to 6.3/year in the past decade, when loiasis became predominant. Cases reported symptoms in >80% of all filarial infections but mansonellosis (45/123 single infections; 37%). Lymphatic filariasis and onchocerciasis cases responded well to conventional therapy. However, 30% of patients with loiasis and mansonellosis experienced treatment failure (with diethylcarbamazine and levamisole-mebendazole, respectively)., Conclusions: The burden and species distribution of filariasis in travelers evolved in the past decades. Most presentations were symptomatic. Case management would benefit from more effective therapies for loiasis and mansonellosis., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: COVID-19 patients experience several features of dysregulated immune system observed in sepsis. We previously showed a dysregulation of several proline-selective peptidases such as dipeptidyl peptidase 4 (DPP4), fibroblast activation protein alpha (FAP), prolyl oligopeptidase (PREP) and prolylcarboxypeptidase (PRCP) in sepsis. In this study, we investigated whether these peptidases are similarly dysregulated in hospitalized COVID-19 patients., Methods: Fifty-six hospitalized COVID-19 patients and 32 healthy controls were included. Enzymatic activities of DPP4, FAP, PREP and PRCP were measured in samples collected shortly after hospital admission and in longitudinal follow-up samples., Results: Compared to healthy controls, both DPP4 and FAP activities were significantly lower in COVID-19 patients at hospital admission and FAP activity further decreased significantly in the first week of hospitalization. While PRCP activity remained unchanged, PREP activity was significantly increased in COVID-19 patients at hospitalization and further increased during hospital stay and stayed elevated until the day of discharge., Conclusion: The changes in activities of proline-selective peptidases in plasma are very similar in COVID-19 and septic shock patients. The pronounced decrease in FAP activity deserves further investigation, both from a pathophysiological viewpoint and as its utility as a part of a biomarker panel., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: To date, both one- and two-stage techniques are used in immediate 'implant-based breast reconstruction' (IBBR) after mastectomy. Because it is still unknown what technique offers the best clinical outcomes, a multicenter retrospective study was conducted to compare both breast reconstruction techniques., Methods: All patients, who underwent a mastectomy followed by immediate one- or two-stage IBBR during 2010 - 2016 were included. Our primary outcome measure was explantation of the 'tissue expander' (TE) and/ or implants within 60 days after breast reconstruction. Secondary outcomes were overall complication rate and secondary corrections., Findings: Among a total of 383 women, TE/ implant explantation rate was higher in one-stage (19.9%) than in two-stage (11.3%) treated patients (p = 0.082). Overall complication rate (35.7% and 19.9% respectively, p = 0.008) and secondary corrections (29.8% and 20.3% respectively, p = 0.156) were also higher in one-stage compared to two-stage IBBR respectively. However, explantation (OR = 1.55; 95%CI = 0.67-3.58, p = 0.301) and complication (OR = 1.85; 95%CI = 0.92-3.37, p = 0.084) rates were comparable in one- and two-stage IBBR in our stratified multivariate logistic regression analyses, when controlling for history of smoking, nipple-sparing mastectomy, neoadjuvant radiation therapy, and removed breast tissue weight. A remarkable outcome in this study is that women treated with prophylactic surgery were more likely to have an explantation of the TE/ implant after a one-stage IBBR (OR = 4.49; 95%CI = 1.10-18.3, p = 0.037) than two-stage IBBR. In contrast, no association between type of IBBR and risk of TE/implants removal was found among women with a therapeutic mastectomy (OR = 0.82; 95%CI = 0.24-2.79, p =  = 0.74)., Conclusion: One- and two-stage IBBR showed a comparable explantation and complication rate in our retrospective study. In one-stage IBBR more secondary corrections were detected. In addition, women who have to decide on a prophylactic mastectomy should be aware of a significantly higher risk of explantation of their implant after one-stage IBBR., Competing Interests: Declaration of Competing Interest None to declare, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection.

A general anti-Baldwin radical 4-exo-dig cyclization from nitrogen-substituted alkynes is reported. Upon reaction with a heteroleptic copper complex in the presence of an amine and under visible light irradiation, a range of ynamides were shown to smoothly cyclize to the corresponding azetidines, useful building blocks in natural product synthesis and medicinal chemistry, with full control of the regioselectivity of the cyclization resulting from a unique and underrated radical 4-exo-dig pathway., (© 2022. The Author(s).)