Neuroborreliosis with involvement of rhombencephalon: A case report.

We describe a case of a 52 year-old woman who was hospitalized with rhombencephalitis caused by Borrelia burgdorferi sensu lato. The patient presented with intermittent fever, dry cough, fatigue, global headache, night sweats, unintentional weight loss, and neurological symptoms like diplopia, tremor, paresthesia and ataxia. Examination of serum and cerebrospinal fluid (CSF) revealed positive Borrelia burgdorferi-specific antibody index and presence of CSF oligoclonal IgG bands, indicating intrathecal synthesis of Borrelia-specific antibodies. The clinical and biochemical picture thus suggested neuroborreliosis. Unexpectedly a magnetic resonance imaging (MRI) scan demonstrated inflammation in rhombencephalon that are extremely rare in patients with neuroborreliosis. The patient was treated with intravenous ceftriaxone with rapid improvement of her symptoms. The MRI findings were in regress six weeks after onset of antibiotic treatment, and normalized after about seven months.

A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics.

Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2.

Norwegian Coronavirus Disease 2019 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with coronavirus disease 2019: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The hypothesis of the study is that treatment with hydroxychloroquine sulphate in hospitalised patients with coronavirus disease 2019 (Covid-19) is safe and will accelerate the virological clearance rate for patients with moderately severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when compared to standard care. Furthermore, we hypothesize that early treatment with hydroxychloroquine sulphate is associated with more rapid resolve of clinical symptoms as assessed by the National Early Warning Score 2 (NEWS2), decreased admission rate to intensive care units and mortality, and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide). TRIAL DESIGN: The study is a two-arm, open label, pragmatic randomised controlled group sequential adaptive trial designed to assess the effect on viral loads and clinical outcome of hydroxychloroquine sulphate therapy in addition to standard care compared to standard care alone in patients with established Covid-19. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), this pragmatic trial can include a larger number of patients over a short period of time and at a lower cost than studies utilizing traditional randomized controlled trial designs with an external study organization. The pragmatic approach will enable swift initiation of randomisation and allocation to treatment. PARTICIPANTS: Patients will be recruited from all inpatients at Akershus University Hospital, Lørenskog, Norway. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly for SARS-CoV-2 positive subjects. All of the following conditions must apply to the prospective patient at screening prior to inclusion: (1) Hospitalisation; (2) Adults 18 years or older; (3) Moderately severe Covid-19 disease (NEWS2 of 6 or less); (4) SARS-CoV-2 positive nasopharyngeal swab; (5) Expected time of hospitalisation > 48 hours; and (6) Signed informed consent must be obtained and documented according to Good Clinical Practice guidelines of the International Conference on Harmonization, and national/local regulations. Patients will be excluded from participation in the study if they meet any of the following criteria: (1) Requiring intensive care unit admission at screening; (2) History of psoriasis; (3) Known adverse reaction to hydroxychloroquine sulphate; (4) Pregnancy; or (5) Prolonged corrected QT interval (>450 ms). Clinical data, including standard hospital biochemistry, medical therapy, vital signs, NEWS2, and microbiology results (including blood culture results and reverse transcriptase polymerase chain reaction [RT-PCR] for other upper airway viruses), will be automatically extracted from the hospital electronic records and merged with the study specific database. INTERVENTION AND COMPARATOR: Included patients will be randomised in a 1:1 ratio to (1) standard care with the addition of 400 mg hydroxychloroquine sulphate (PlaquenilTM) twice daily for seven days or (2) standard care alone. MAIN OUTCOMES: The primary endpoint of the study is the rate of decline in SARS-CoV-2 viral load in oropharyngeal samples as assessed by RT-PCR in samples collected at baseline, 48 and 96 hours after randomization and administration of drug for the intervention arm. Secondary endpoints include change in NEWS2 at 96 hours after randomisation, admission to intensive care unit, mortality (in-hospital, and at 30 and 90 days), duration of hospital admission, clinical status on a 7-point ordinal scale 14 days after randomization ([1] Death [2] Hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation [3] Hospitalised, on non-invasive ventilation or high flow oxygen devices [4] Hospitalized, requiring supplemental oxygen [5] Hospitalised, not requiring supplemental oxygen [6] Not hospitalized, but unable to resume normal activities [7] Not hospitalised, with resumption of normal activities), and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide) at 96 hours after randomization. RANDOMISATION: Eligible patients will be allocated in a 1:1 ratio, using a computer randomisation procedure. The allocation sequence has been prepared by an independent statistician. BLINDING (MASKING): Open label randomised controlled pragmatic trial without blinding, no active or placebo control. The virologist assessing viral load in the oropharyngeal samples and the statistician responsible for analysis of the data will be blinded to the treatment allocation for the statistical analyses. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is a group sequential adaptive trial where analyses are planned after 51, 101, 151 and 202 completed patients, with a maximum sample size of 202 patients (101 patients allocated to intervention and standard care and 101 patients allocated to standard care alone). TRIAL STATUS: Protocol version 1.3 (March 26, 2020). Recruitment of first patient on March 26, 2020, and 51 patients were included as per April 28, 2020. Study recruitment is anticipated to be completed by July 2020. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04316377. Trial registered March 20, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Predictors of one-year all-cause mortality and infection-related mortality in patients with Staphylococcus aureus bacteraemia.

OBJECTIVES: Staphylococcus aureus bacteraemia (SAB) is a common infection associated with significant short-term mortality. Little is known about long-term prognosis. The aim of this study was to determine one-year all-cause mortality and infection-related mortality and associated predictors. METHODS: Data from 303 consecutive patients with SAB were prospectively collected from March 2011 to February 2014. All patients were followed one year or until death. RESULTS: One-year all-cause- and infection-related mortality were 36.7% and 20.8%, respectively. For all-cause mortality, in multivariable logistic regression analysis, age 70-79 years (OR 3.9; 95% CI 1.7-9.1; p = .001), Charlson Comorbidity index ≥3 (OR 6.9; 95% CI 2.7-17.3; p < .001), healthcare-associated infection (OR 2.3; 95% CI 1.1-4.9; p = .03) and severe sepsis (OR 3.6; 95% CI 1.8-7.1; p < .001) were independent predictors of outcome. For infection-related mortality, the predictors were similar, except for healthcare-associated infection that lost significance. The vast majority (89%) of infection-related deaths occurred within 30 days. CONCLUSIONS: This study demonstrates additional significant all-cause mortality in patients with SAB beyond 30 days to one year, mainly driven by high age and comorbidity. As a result, SAB can be considered an indirect marker of high risk of death in these patients. Follow-up beyond 30 days does not add significant information with respect to infection-related mortality.

Low use of surveillance and early diagnosis of hepatocellular carcinoma in Norway--a population-based cohort study.

BACKGROUND AND AIMS: Curative treatment of hepatocellular carcinoma (HCC) is dependent on early diagnosis. Surveillance of patients at high risk for HCC is a key determinant to achieve this goal, but may be an underutilized tool. The aim of this study was to determine the rate of pre-diagnosis surveillance in patients with HCC in a large population-based cohort and to assess to what extent cirrhosis was known prior to the diagnosis of HCC. METHODS: All patients diagnosed with HCC during 2000-2009 in The South-Eastern Regional Health Authority, representing 56% of the Norwegian population, were identified from The National Cancer Registry and the medical records were reviewed. RESULTS: Fifteen out of 486 patients (3%) were diagnosed by surveillance. Potential curative treatment was offered to 58% of the patients who underwent surveillance as opposed to 15% in the non-surveillance group. Only age ≤ 65 years was an independent predictor of screening in a multivariate model. Almost two thirds of the patients with cirrhosis were unrecognized prior to the HCC diagnosis. Two hundred and fourteen patients (44%) were non-cirrhotics. CONCLUSION: Regular HCC surveillance in at-risk populations is virtually not applied in Norway and this may contribute to inferior overall survival. Failure to recognize cirrhosis and a high rate of HCC in non-cirrhotic patients will be limiting factors for the overall effectiveness of a potential surveillance program.

Molecular characterization of methicillin-sensitive Staphylococcus aureus isolates from bacteremic patients in a Norwegian University Hospital.

Staphylococcus aureus bacteremia is common in both nosocomial and community settings, and the pathogenicity of the microbe depends upon a large repertoire of virulence factors. S. aureus bacteremia isolates (n = 126) were characterized using DNA microarrays. Clonal complexes 5, 8, 15, 30, and 45 accounted for 74.6% of the isolates. We identified geographical differences in dominating clones and toxin gene profiles. One isolate was methicillin resistant. Potential associations between age and genotype were detected.

Genotyping of 353 Staphylococcus aureus bloodstream isolates collected between 2004 and 2009 at a Norwegian university hospital and potential associations with clinical parameters.

We analyzed 353 Staphylococcus aureus bloodstream isolates from 2004 to 2009 to identify dominant genotypes, changes over time, and associations between genotype, phenotype, and clinical parameters. The isolates were genotyped with regard to spa type and presence of Panton-Valentine leukocidin and toxic shock syndrome toxin 1-encoding genes. A high level of genetic diversity was detected. All but three isolates were methicillin sensitive. Interestingly, spa clonal complex 021 showed a weak association with higher all-cause hospital mortality.

Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.

OBJECTIVES: Two functional genetic variants in the inosine triphosphatase (ITPA) gene have been shown to be strongly associated with protection from ribavirin (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where available data are scarce. A second objective was to determine whether a protective association translated into the need for RBV reduction and hence a possible impact on treatment response. METHODS: Overall, 457 patients were recruited from two trials of genotype 2/3 patients treated with pegylated interferon α-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped and a composite ITPAase deficiency variable was graded according to the two single nucleotide polymorphisms. The primary endpoints were hemoglobin (Hb) decline from baseline and Hb decline of more than 3 g/dl at week 4. RESULTS: Both single nucleotide polymorphisms and the composite ITPAase deficiency variable were strongly and independently associated with protection from a decline in Hb at week 4 in multivariate linear regression models (Prs1127354=7.0×10, Prs7270101=0.0036, PITPase deficiency variable =6.3×10). Patients with any degree of reduced ITPAase activity were less likely to have their RBV dose reduced (odds ratio 0.39, 95% confidence interval 0.16-0.96, P=0.040), although this did not translate into increased rapid viral response or sustained viral response (Prvr=0.93, Psvr=0.22). CONCLUSION: We have confirmed a strong association between functional ITPA variants and RBV-induced hemolysis and showed protection from RBV dose reduction, although this did not translate into increased rapid viral response or sustained viral response.

[Immune reconstitution inflammatory syndrome and treatment of HIV infection]. / Immunrekonstitusjonssyndrom ved behandling av hivinfeksjon.

BACKGROUND: HAART (highly active antiretroviral therapy) may trigger a condition known as IRIS (immune reconstitution inflammatory syndrome); i.e. a paradoxical reaction to latent infections associated with reconstitution of the immune system. The article provides an overview of the syndrome and discusses diagnosis, risk factors and management. MATERIAL AND METHODS: The basis for the article was literature identified through non-systematic searches in PubMed and clinical experience. RESULTS: IRIS typically occurs some weeks to months after initiation of HAART, usually in association with mycobacterial infections, cytomegalovirus, Cryptococcus neoformans and Pneumocystis jirovecii. In principle, any pathogen may cause a similar inflammatory response. Risk factors for IRIS include severe immunodeficiency, high antigen burden and rapid immune response to HAART. The prognosis is good. However, treatment of infections must not delay the initiation of HAART, as such a delay may increase morbidity and mortality. HAART should be continued unless symptoms are life-threatening or likely to cause permanent sequelae. Corticosteroids may be helpful in cases with lesions in the central nervous system, obstructive lymph nodes or increasing respiratory symptoms. INTERPRETATION: Treatment of HIV infection has improved substantially, which implies an increased number of patients developing IRIS. A quick diagnosis and correct and timely treatment of opportunistic infections is important for the prognosis.

Short-term success, but long-term treatment failure with linezolid for enterococcal endocarditis.

We report a case of linezolid treatment failure for Enterococcus faecalis endocarditis. Despite success during and shortly after treatment, the patient had a relapse after 7 weeks. Due to prior anaphylactic reaction to penicillin, desensitization was performed, and successful penicillin therapy given. The efficacy of linezolid for enterococcal endocarditis remains questionable.

Infectious tenosynovitis and osteomyelitis caused by Mycobacterium nonchromogenicum.

Infections due to Mycobacterium terrae complex are rare. We report a severe case of chronic tenosynovitis and osteomyelitis of the hand caused by Mycobacterium nonchromogenicum requiring second ray finger amputation.