Lactococcus garvieae, an unusual pathogen in infective endocarditis: case report and review of the literature

Lactococcus garvieae is an unusual cause of infective endocarditis (IE). No current diagnostic and therapeutic guidelines are available to treat IE caused by these organisms. Based on a case report, we provide a review of the literature of IE caused by L. garvieae and highlight diagnostic and treatment challenges of these infections and implications for management. A 50-year-old Asian male with mitral prosthetic valve presented to the hospital with intracranial haemorrhage, which was successfully treated. Three weeks later, he complained of generalized malaise. Further work up revealed blood cultures positive for Gram-positive cocci identified as L. garvieae by MALDI-TOF. An echocardiogram confirmed the diagnosis of IE. Susceptibility testing showed resistance only to clindamycin. Vancomycin plus gentamicin were started as empirical therapy and, subsequently, the combination of ceftriaxone plus gentamicin was used after susceptibility studies were available. After two weeks of combination therapy, ceftriaxone was continued as monotherapy for six additional weeks with good outcome. Twenty-five cases of IE by Lactococcus garvieae have been reported in the literature. Compared to other Gram-positive cocci, L. garvieae affects more frequently patients with prosthetic valves. IE presents in a subacute manner and the case fatality rate can be as high as 16%, comparable to that of streptococcal IE (15.7%). Reliable methods for identification of L. garvieae include MALDI-TOF, 16S RNA PCR, API 32 strep kit and BD Automated Phoenix System. Recommended antimicrobials for L. garvieae IE are ampicillin, amoxicillin, ceftriaxone or vancomycin in monotherapy or in combination with gentamicin

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

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Effects of COVID-19 Lockdown on Tumour Burden of Melanoma and Cutaneous Squamous Cell Carcinoma.

The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer

Switching TNF antagonists in patients with chronic arthritis: An observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020