Cerebral malaria (CM) is an acute encephalopathy in humans due to the infection with
Plasmodium falciparum. Neuro-cognitive impairment following CM occurs in about 10% of the treated survivors, while ...the precise pathophysiological mechanism remains unknown. Metallothionein I + II (MT-I + II) are increased during CNS pathology and disorders. As previously shown, MT-I + II are neuroprotective through anti-inflammatory, antioxidant and antiapoptotic functions. We have analyzed neuronal apoptosis and MT-I + II expression in brains of mice with experimental CM.
C57BL/6j mice, infected with
Plasmodium berghei ANKA, were studied on day 7, day 9, and when presenting signs of CM on days 10–12. We investigated brain histopathology by immunohistochemistry and TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling). For statistics, we used quantitation (cellular counts) of the analyzed variables.
During CM, we observed significant inflammatory responses of F4/80+ microglia/macrophages and GFAP+ reactive astrocytes and increased immunoreactivity of 8-oxoguanine (marker of oxidative stress). As novel findings, we show: (1) a localized CM-induced neuronal apoptosis (detected by TUNEL) indicating severe and irreversible pathology. (2) A significant increase in MT-I + II expression in reactive astrocytes, macrophages/microglia and vascular endothelium.
This is the first report showing apoptosis of neurons in CM by TUNEL, pointing out a possible pathophysiological mechanism leading to persisting brain damage. The possible neuroprotective role of MT-I + II during CM deserves further attention.
We describe the clinical course of a 60-year old male admitted with Staphylococcus aureus bacteremia and back-pain. The patient was suspected of having spondylitis and treated as such with ...antibiotics; however, both fluorine-18 fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography and magnetic resonance imaging (MRI) with iv contrast showed significant inflammation of muscles and subcutaneous soft tissue in relation to the patients back and left shoulder, but no signs of the working diagnosis of spondylitis. The unusual location of the infection was not explained until a few days prior to being discharged when the patient reported visits to a local physiotherapist where he would have acupuncture performed for non-specific back pain. His last acupunctural procedure had been performed 6 days prior to admission. This case is, to our knowledge, the first to show muscular inflammation on both 18-F-FDG PET/CT and MRI following acupuncture due to S. aureus. This case highlights the need for clinicians to search for alternative explanations when imaging does not support the diagnosis.
Purpose
Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized ...COVID-19 patients and the development of venous thromboembolic events (VTE).
Methods
A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores).
Results
Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses.
Conclusion
In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating.
Clinicaltrials.gov ID
NCT04377035
Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive ...impairment in about 10% of the survivors. Erythropoietin (Epo) has - besides of its well known haematopoietic properties - significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. The neurobiological responses to exogenously injected Epo during murine CM were examined.
Female C57BL/6j mice (4-6 weeks), infected with Plasmodium berghei ANKA, were treated with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene expression in brain tissue was measured by real time PCR.
Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect appeared to be independent of the haematopoietic effect.
These results and its excellent safety profile in humans makes rhEpo a potential candidate for adjunct treatment of CM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Cellulitis ranks among the most frequent infections, and antibiotic treatment is the accepted mainstay of therapy. There is disagreement on the guidelines for the use of compression ...bandaging as supplementary treatment, and the evidence within the field is scarce.
Objectives
To determine whether compression bandaging impairs microcirculation in patients with cellulitis of the lower leg, thereby having a negative impact on the supply of oxygen, nutritional components, and antibiotics.
Materials and Methods
Adult patients were prospectively enrolled for compression bandaging in addition to antibiotic treatment. The peripheral blood flow rate was measured before and after application of the compression bandage and on the following day. For this, we applied the heat-washout method, which has previously been shown to provide an accurate estimate of peripheral microcirculation.
Results
Comparing the blood flow rate before and after application of the compression bandage showed no significant change and therefore no alteration in microcirculation (
p
= 0.61).
Conclusion
Compression bandaging of the lower leg does not impair microcirculation in patients with cellulitis. This strongly indicates that compression bandaging can play a positive role as supportive treatment in addition to standard antibiotic therapy.
OBJECTIVES:To describe changes in the prevalence of comorbidities and risk factors among HIV-positive individuals in the EuroSIDA study.
DESIGN:Comparison of two cross-sectional cohorts of ...HIV-positive adults under active follow-up in 2006 and 2014.
METHODS:Baseline demographics and prevalence of comorbidities were described. Factors associated with the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD) were assessed by logistic regression modelling using generalized estimating equations.
RESULTS:Nine thousand, seven hundred and ninety-eight individuals were under active follow-up in EuroSIDA during 2006 and 12 882 during 2014. Compared with study participants in 2006, those in 2014 were older median age 48.6 years (IQR 40.3–55.1) vs. 43.1 years (37.2–50.0) in 2006 and had higher prevalence of hypertension (59.6 vs. 47% in 2006), diabetes (6.3 vs. 5.4%), CKD (6.9 vs. 4.1%) and CVD (5.0 vs. 3.7%). Individuals in the 2014 cohort had higher odds for CKD (unadjusted OR 2.62, 95% CI 2.30–2.99, P < 0.0001) and CVD (OR 1.88, CI 1.68–2.10, P < 0.0001), but after multivariable adjustment for age group, comorbidities and other factors, year of cohort was no longer significantly associated with the odds of CKD adjusted OR (aOR) 0.97, CI 0.52–1.82, P = 0.92) or of CVD (aOR 0.94, CI 0.54–1.63, P = 0.82).
CONCLUSION:Between 2006 and 2014, the population aged and experienced an overall higher prevalence of non-AIDS comorbidities, including CKD and CVD. The increase in CVD could be explained by the aging population, and the increase in CKD by aging and changes in other factors. Treatment strategies balancing HIV outcomes with long-term management of comorbidities remain a priority.
Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe ...the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors.
International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections.
Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28–40; range 19–84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 50% of 62) than among cis women and non-binary individuals (six 8% of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1–200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported.
The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high.
None.
Abstract
Background
There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We ...sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone.
Methods
Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI).
Results
The 30-days mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI: .38–.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36; 95% CI: .29–.46).
Conclusions
Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.
Treatment of moderate to severe coronavirus disease 2019 (COVID-19) with remdesivir and dexamethasone was associated with a lower risk of mechanical ventilation and a significant better overall 30-day survival as compared to standard care alone.
SARS‐CoV‐2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients ...might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long‐term SARS‐CoV‐2 infection with the pre‐VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi‐species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS‐CoV‐2 among immunocpromised patients.
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