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Background Streptococci are a common cause of infective endocarditis (IE). We aimed to evaluate the performance of the HANDOC score to identify patients at high risk for IE and the Duke clinical criteria of the European Society of Cardiology (ESC; 2015 and 2023 versions) and the 2023 version from the International Society of Cardiovascular Infectious Diseases (ISCVID) in diagnosing IE among patients with streptococcal bacteremia. Methods This retrospective study included adult patients with streptococcal bacteremia hospitalized at Lausanne University Hospital. Episodes were classified as IE by the Endocarditis Team. A HANDOC score >2 classified patients as high risk for IE. Results Among 851 episodes with streptococcal bacteremia, IE was diagnosed in 171 episodes (20%). Among 607 episodes with non-β-hemolytic streptococci, 213 (35%) had HANDOC scores >2 points; 132 (22%) had IE. The sensitivity of the HANDOC score to identify episodes at high risk for IE was 95% (95% confidence interval [CI], 90%–98%), the specificity 82% (95% CI, 78%–85%), and the negative predictive value (NPV) 98% (95% CI, 96%–99%). 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria classified 114 (13%), 145 (17%), and 126 (15%) episodes as definite IE, respectively. Sensitivity (95% CI) for the 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria was calculated at 65% (57%–72%), 81% (74%–86%), and 73% (65%–79%), respectively, with specificity (95% CI) at 100% (98%–100%), 99% (98%–100%), and 99% (98%–100%), respectively. Conclusions The HANDOC score showed an excellent NPV to identify episodes at high risk for IE. Among the different versions of the Duke criteria, the 2023 Duke-ISCVID version fared better for the diagnosis of IE among streptococcal bacteremia. [ABSTRACT FROM AUTHOR]

Cryptic Aspergillus species are increasingly recognized as pathogens involved in human disease. They are ubiquitarian fungi with high tenacity in their environment and can express various resistance mechanisms, often due to exposure to antifungal agents employed in agriculture and farming. The identification of such species is increasing thanks to molecular techniques, and a better description of this type of pathogen is granted. Nevertheless, the number of species and their importance in the clinical setting still need to be well studied. Furthermore, their cross-sectional involvement in animal disease, plants, and human activities requires a multidisciplinary approach involving experts from various fields. This comprehensive review aims to provide a sharp vision of the cryptic Aspergillus species, from the importance of correct identification to the better management of the infections caused by these pathogens. The review also accentuates the importance of the One Health approach for this kind of microorganism, given the interconnection between environmental exposure and aspergillosis, embracing transversely the multidisciplinary process for managing the cryptic Aspergillus species. The paper advocates the need for improving knowledge in this little-known species, given the burden of economic and health implications related to the diffusion of these bugs. [ABSTRACT FROM AUTHOR]

To the Editor: Invasive meningococcal disease is usually defined by the occurrence of meningitis or septicemia. Pericarditis might occur during the course of invasive infection. This clinical picture, defined as [...]

Background: Limitations of hair restoration procedures are the amount of hairs available and the invasiveness of follicular harvesting.Objective: The aim of this study was to compare conventional human micrografts and plucked hair follicles in an in vitro model in order to test hair growth rates for experimentally assessing the soundness of plucked follicle use in hair transplantation procedures.Methods and Materials: A total of 100 conventional one-hair micrografts (group A; control) and a total of 80 plucked hair follicles (group B; experimental) were obtained from 14 healthy male patients. The length of each graft was measured immediately following isolation and at the end of the 10-day culture period. The Kruskal-Wallis one-way analysis of variance by ranks test was used in order to statistically analyze the data obtained.Results: A statistically significant difference was found between the growth rate of micrografts in control (mean 10-day shaft growth rate = 0.30mm) and experimental (mean 10-day shaft growth rate = 0.36mm) groups.Conclusion: The obtained data shows a higher plucked hair follicle growth rate compared to one-hair micrografts, which leads us to believe that plucked micrografts could be a useful and less invasive adjunct in the field of hair transplantation surgery. [ABSTRACT FROM AUTHOR]

During COVID19 pandemic, SARS-CoV-2 rapid antigen tests (RATs) were marketed with minimal or no performance data. We aimed at closing this gap by determining technical sensitivities and specificities of 30 RATs prior to market release. We developed a standardized technical validation protocol and assessed 30 RATs across four diagnostic laboratories. RATs were tested in parallel using the Standard Q® (SD Biosensor/Roche) assay as internal reference. We used left-over universal transport/optimum media from nasopharyngeal swabs of 200 SARS-CoV-2 PCR-negative and 100 PCR-positive tested patients. Transport media was mixed with assay buffer and applied to RATs according to manufacturer instructions. Sensitivities were determined according to viral loads. Specificity of at least 99% and sensitivity of 95%, 90%, and 80% had to be reached for 107, 106, 105 virus copies/mL, respectively. Sensitivities ranged from 43.5% to 98.6%, 62.3% to 100%, and 66.7% to 100% at 105, 106, 107 copies/mL, respectively. Automated assay readers such as ExDia or LumiraDx showed higher performances. Specificities ranged from 88.8% to 100%. Only 15 of 30 (50%) RATs passed our technical validation. Due to the high failure rate of 50%, mainly caused by lack of sensitivity, we recommend a thorough validation of RATs prior to market release. [ABSTRACT FROM AUTHOR]

Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples. We conducted a prospective observational study among COVID-19 hospitalized patients between 10 December 2020 and 1 February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland, Basel, Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Daejeon, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland). A total of 58 paired NP-saliva specimens were collected. A total of 32 of 58 (55%) patients were hospitalized in the intensive care unit, and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively, whereas the specificity of these RT-PCRs assays was 100%. The NP RATs exhibited much lower diagnostic performance, with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays, respectively, when a wet-swab approach was used (i.e., when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4% and 8%) when applied to salivary swabs. Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RATs are not appropriate for hospitalized patients. [ABSTRACT FROM AUTHOR]

Following the Swiss Federal Office of Public Health (FOPH) authorization of the rapid antigen test (RAT), we implemented the use of the RAT in the emergency ward of our university hospital for patients' cohorting. RAT triaging in association with RT-PCR allowed us to promptly isolate positive patients and save resources. Among 532 patients, overall sensitivities were 48.3% for Exdia and 41.2% for Standard Q®, PanbioTM and BD Veritor™. All RATs exhibited specificity above 99%. Sensitivity increased to 74.6%, 66.2%, 66.2% and 64.8% for Exdia, Standard Q®, PanbioTM and BD Veritor™, respectively, for viral loads above 105 copies/mL, to 100%, 97.8%, 96.6% and 95.6% for viral loads above 106 copies/mL and 100% for viral loads above 107 copies/mL. Sensitivity was significantly higher for patients with symptoms onset within four days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with the evolution of symptoms longer than four days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Among COVID-19 asymptomatic patients, sensitivity was 33%. All Immunoglobulin-A-positive patients resulted negative for RAT. The RAT might represent a useful resource in selected clinical settings as a complementary tool in RT-PCR for rapid patient triaging, but the lower sensitivity, especially in late presenters and COVID-19 asymptomatic subjects, must be taken into account. [ABSTRACT FROM AUTHOR]

Aims of the Study: Invasive mould infections are life-threatening complications in patients with haematologic cancer and chemotherapy-induced neutropenia. While invasive aspergillosis represents the main cause of invasive mould infections, non-Aspergillus mould infections, such as mucormycosis, are increasingly reported. Consequently, their local epidemiology should be closely monitored. The aim of this study was to investigate the causes of an increased incidence of non-Aspergillus mould infections in the onco-haematology unit of a Swiss tertiary care hospital., Methods: All cases of proven and probable invasive mould infections were retrospectively identified via a local registry for the period 2007-2021 and their incidence was calculated per 10,000 patient-days per year. The relative proportion of invasive aspergillosis and non-Aspergillus mould infections was assessed. Factors that may affect invasive mould infections' incidence, such as antifungal drug consumption, environmental contamination and changes in diagnostic approaches, were investigated., Results: A significant increase of the incidence of non-Aspergillus mould infections (mainly mucormycosis) was observed from 2017 onwards (Mann and Kendall test p = 0.0053), peaking in 2020 (8.62 episodes per 10,000 patient-days). The incidence of invasive aspergillosis remained stable across the period of observation. The proportion of non-Aspergillus mould infections increased significantly from 2017 (33% vs 16.8% for the periods 2017-2021 and 2007-2016, respectively, p = 0.02). Building projects on the hospital site were identified as possible contributors of this increase in non-Aspergillus mould infections. However, novel diagnostic procedures may have improved their detection., Conclusions: We report a significant increase in non-Aspergillus mould infections, and mainly in mucormycosis infections, since 2017. There seems to be a multifactorial origin to this increase. Epidemiological trends of invasive mould infections should be carefully monitored in onco-haematology units in order to implement potential corrective measures.

In November 2021, the World Health Organization declared the Omicron variant (B.1.1.519) a variant of concern. Since then, worries have been expressed regarding the ability of usual diagnostic tests to detect the Omicron variant. In addition, some recently published data suggested that the salivary reverse transcription (RT)-PCR might perform better than the current gold standard, nasopharyngeal (NP) RT-PCR. In this study, we aimed to compare the sensitivities of nasopharyngeal and saliva RT-PCR and assess the diagnostic performances of rapid antigen testing (RAT) in nasopharyngeal and saliva samples. We conducted a prospective clinical study among symptomatic health care professionals consulting the occupational health service of our hospital for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening and hospitalized patients in internal medicine/intensive care wards screened for SARS-CoV-2 with COVID-19-compatible symptoms. A composite outcome considering NP PCR and/or saliva PCR was used as a reference standard to define COVID-19 cases. A total of 475 paired NP/saliva specimens have been collected with a positivity rate of 40% ( n  = 192). NP and salivary RT-PCR exhibited sensitivities of 98% (95% CI, 94 to 99%) and 87% (95% CI, 81 to 91%), respectively, for outpatients ( n  = 453) and 94% (95% CI, 72 to 99%) and 69% (95% CI, 44 to 86%), respectively, for hospitalized patients ( n  = 22). Nasopharyngeal rapid antigen testing exhibited much lower diagnostic performances (sensitivity of 66% and 31% for outpatients and inpatients, respectively), while saliva RAT showed a sensitivity of less than 5% in both groups. Nasopharyngeal RT-PCR testing remains the gold standard for SARS-CoV-2 Omicron variant screening. Salivary RT-PCR can be used as an alternative in case of contraindication to perform NP sampling. The use of RAT should be limited to settings where access to molecular diagnostic methods is lacking. IMPORTANCE The Omicron variant of concern spread rapidly since it was first reported in November 2021 and currently accounts for the vast majority of new infections worldwide. Recent reports suggest that saliva sampling might outweigh nasopharyngeal sampling for the diagnosis of the Omicron variant. Nevertheless, data investigating the best diagnostic strategy specifically for the Omicron variant of concern remain scarce. This study fills this gap in current knowledge and elucidates the question of which strategy to use in which patient. It provides a new basis for further improving COVID-19 screening programs and managing patients suspected to have COVID-19.

Introduction: Effective treatment of bloodstream infections (BSIs) is relying on rapid identification of the causing pathogen and its antibiotic susceptibility. Still, most commercially available antibiotic susceptibility testing (AST) methods are based on monitoring bacterial growth, thus impacting the time to results. The Resistell AST is based on a new technology measuring the nanomotion caused by physiologically active bacterial cells and detecting the changes in nanomotion caused by the exposure to a drug., Methods and Analysis: This is a single-centre, prospective, cross-sectional, single-arm diagnostic accuracy study to determine the agreement of the Resistell AST on Gram-negative bacteria isolated from blood cultures among patients admitted to a tertiary-care hospital with the reference method. Up to 300 patients will be recruited. Starting with a pilot phase, enrolling 10%-20% of the subjects and limited to Escherichia coli BSI tested for ceftriaxone susceptibility, the main phase will follow, extending the study to Klebsiella pneumoniae and ciprofloxacin., Ethics and Dissemination: This study has received ethical approval from the Swiss Ethics Committees (swissethics, project 2020-01622). All the case report forms and clinical samples will be assigned a study code by the local investigators and stored anonymously at the reference centre (Lausanne University Hospital). The results will be broadly distributed through conference presentations and peer-reviewed publications., Trial Registration Number: ClinicalTrials.gov Registry (NCT05002413)., Competing Interests: Competing interests: GG is medical advisor for Resistell. AV, AL, ED, AS, DC and GJ are employed by Resistell. GC, AK, SK and JD have no conflict of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: While laboratories have been facing limited supplies of reagents for diagnostic tests throughout the course of the COVID-19 pandemic, national and international health plans, as well as billing costs, have been constantly adjusted in order to optimize the use of resources. We aimed to assess the impact of SARS-CoV-2 test costs and reimbursement tariff adjustments on diagnostic strategies in Switzerland to determine the advantages and disadvantages of different costs and resource saving plans., Materials and Methods: We specifically assessed the cost of diagnostic SARS-COV-2 RT-PCR using five different approaches: i) in-house platform, ii) cobas 6800® (Roche, Basel, Switzerland), iii) GeneXpert® SARS-CoV-2 test (Cepheid, Sunnyvale, CA, USA), iv) VIASURE SARS-CoV-2 (N1 + N2) Real-Time PCR Detection Kit for BD MAX™ (Becton Dickinson, Franklin Lake, NJ, USA), v) cobas® Liat® SARS-CoV-2 & Influenza A/B (Roche, Basel, Switzerland). We compared these costs to the evolution of the reimbursement tariffs., Results: The cost of a single RT-PCR test varied greatly (as did the volume of tests performed), ranging from as high as 180 CHF per test at the beginning of the pandemic (February to April 2020) to as low as 82 CHF per test at the end of 2020. Depending on the time period within the pandemic, higher costs did not necessarily mean greater benefits for the laboratories. The costs of molecular reagents for rapid tests were higher than of those for classic RT-PCR platforms, but the rapid tests had reduced turnaround times (TATs), thus improving patient care and enabling more efficient implementation of isolation measures, as well as reducing the burden of possible nosocomial infections. At the same time, there were periods when the production or distribution of these reagents was insufficient, and only the use of several different molecular platforms allowed us to sustain the high number of tests requested., Conclusions: Cost-saving plans need to be thoroughly assessed and constantly adjusted according to the epidemiological situation, the clinical context and the national resources in order to always guarantee that the highest performing diagnostic solutions are available. Not all cost-saving strategies guarantee good analytical performance.

Objectives: Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands., Methods: In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to non-infected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection., Results: We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66-3.09) and 1.32 (1.06-1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48-2.41)., Conclusions: In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A low CD4/CD8 ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 ratio normalization with efavirenz, which was driven by a greater CD8 + T-cell decline., (Copyright © 2017 American Society for Microbiology.)

Unlabelled: Over the years, different kinds of hair transplantation have been compared in an attempt to overcome male pattern alopecia and, at the same time, maximize both the survival and growth rate of grafted hair. In this study, we have assessed the survival and growth rate of follicular units (FU) in an in vitro model, as compared with that of conventional hair micrografts, to experimentally evaluate and elaborate on the differences between these 2 approaches in hair transplantation procedures., Methods: Group A (control; n = 100 follicles) was composed of hair micrografts, whereas FUs were assigned to Group B (experimental; n = 100 follicles, n = 35 FUs). Each group was cultured for a period of 10 days; the total stretch of follicles was measured soon after the harvest and 10 days later. The Kruskal-Wallis one-way analysis of variance on ranks test was used to perform statistical analysis., Results: The growth rate of follicles from Group A (mean 10-day shaft growth rate = 0.30 mm) proved to be statistically different compared with that of Group B (mean 10-day shaft growth rate = 0.23 mm). Conversely, our data did not show any significant difference between the survival rate of hair grafts from these 2 groups., Conclusions: Our data highlighted a reduced FU shaft growth compared with that of hair micrografts, corroborating, to a certain extent, the hypothesis that a significant amount of adipose tissue surrounding the follicle included in the graft may result in an inadequate nourishment supply to follicular cells.

Aim: Adipose tissue represent an alternative source of multipotent stem cells with characteristics similar to bone marrowderived mesenchymal stem cells (BMSCs), easier to isolate and effective in wound healing enhancement., Material of Study: Each patient being considered for stem cells graft was subjected to a conventional liposuction procedure (local anaesthesia, aspirated volume about 80cc), in order to isolate a pellet of adipose-derived stem cells (ASCs), which was then mixed with the platelet-rich plasma (PRP) previously collected, in order to obtain an enhanced-ASCs- PRP (e-PRP), now ready for grafting in the context of skin edges as well as at the bottom of the lesion itself., Results: Flow cytometric analysis performed on the pellet obtained with our isolation process, showed that a mean of 5 x 105 ASCs (range: 4,0-6,0 x 105, SD: ± 1 x 105) were collected from 80 ml of adipose tissue, harvested with standard wet liposuction procedure. It represented the 5% of all sample cells (1 x 107), while the others 95% were mostly being blood-derived and endothelial cells., Discussion: By now, the most used isolation protocols take about two hours due to the complex isolation procedure, requiring both animal-derived reagents and collagenase. The amount of ASCs obtained with our isolation process is sufficient to be directly engrafted in the wound without the need of in vitro expansion but, neither serum nor animalderived reagents are used, and it takes only 15' minutes., Conclusion: ASCs application is an innovative, effective approach in the treatment of chronic wounds.

Aim: The aim of this study is to prove the therapeutic effectiveness of nerve decompression, performed endoscopically for frontal migraine and by open surgery for occipital migraine., Materials and Methods: Twenty patients were enrolled and underwent surgery for endoscopic resection of the glabellar muscle group, including the corrugator supercilii, depressor supercilii, and procerus muscles, while the occipital decompression was performed in open surgery through decompression of occipital nerves from occipital, semispinalis capitis, trapezius and sternocleidomastoid muscles. Every patient was diagnosed with: migraine without aura, chronic tensiontype headache and new daily persistent headache, refractory to medical management., Results: Analyzing the answers given by the patients to validated questionnaires, 9 referred alleviation of migraine symptoms (45%), 8 described elimination of their migraine headaches (40%) while 3 didn't report any improvement., Discussion: Our data confirmed the results of previous studies, pointing out the effectiveness of trigeminal branches and occipital nerves (trigger points) decompression from the surrounding muscles. Moreover, our technique has the same results but it's less invasive and has less collateral effects., Conclusions: Our results highlight migraine surgery as an effective treatment for patients with migraine headaches who do not tolerate or do not wish to continue medical interventions., Key Words: Endoscopic surgery, Headache migraine.

Background: Purse-string suture is a simple technique that can be used to reduce the surface area of circular wounds in an effort to obtain minimal scarring. In this report, we provide evidence of the effectiveness of the purse-string suture as a stand-alone procedure that allows a permanent primary complete closure of small to moderate skin defects. The procedure is used primarily for the repair of skin defects due to cutaneous tumor excision in older patients., Methods: The purse-string suture is executed by using a 1-0 absorbable suture, always by exiting and reentering intradermally and never penetrating the epidermis, in a circumferential fashion., Results: The immediate postoperative folds flatten in about a 4-week postoperative time span, and the resulting scar is the smallest obtainable., Conclusions: The round block purse-string suture is a simple technique which allows complete closure of skin defects without importing tissue from a distance, and it can be particularly suitable for older patients because of their skin laxity.