Abstract
Background
Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate ...whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome.
Methods
We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics.
Results
Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% 95% confidence interval (CI) − 15.7 to 22.7;
P
= 0.703, adjusted OR 1.03 95%CI 0.35–3.06;
P
= 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 95%CI 0.06–0.68;
P
= 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed.
Conclusions
Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration.
Clinical trial registration
clinicaltrials.gov identifier
NCT03345992
registered 17 November 2017; EudraCT 2017-001056-55.
INTRODUCTION: COVID-19-associated pulmonary aspergillosis (CAPA) is a serious complication affecting patients with severe SARS-CoV-2 infection, and is associated with increased mortality.
OBJECTIVE: ...The objective of this study was to investigate potential risk factors, and to estimate the incidence and mortality in patients diagnosed with CAPA.
METHODS: A single-center retrospective observational study was conducted on patients admitted to the intensive care unit (ICU) with severe COVID-19 from October 2020 to May 2022. Patients with deterioration of their clinical status were evaluated with serum galactomannan (GM) for probable CAPA. Baseline demographic patient characteristics, vaccination status, and time period during which each patient was infected with SARS-CoV-2 were obtained, and risk stratification according to underlying comorbidities was performed in an effort to assess various risk factors for CAPA. The incidence of CAPA in the entire cohort was measured, and mortality rates in the CAPA and non-CAPA groups were calculated and compared.
RESULTS: Of 488 patients admitted to the ICU, 95 (19.4%) had deterioration of their clinical status, which prompted testing with serum GM. Positive serum testing was observed in 39/95 patients, with an overall CAPA incidence in the entire study cohort reaching 7.9% (39/488). The mortality rate was 75% (42/56) in the non-CAPA group that was tested for serum GM, and 87.2% (34/39) in the CAPA group (P = 0.041). Multivariable Cox regression hazard models were tested for 28- and 90-day survival from ICU admission. An invasive pulmonary aspergillosis (IPA) risk-stratified cox regression model corrected for the SARS-CoV-2 variant of the patient identified the diagnosis of probable CAPA and elevated procalcitonin (PCT) levels measured at least 10 days after ICU admission, as significantly associated with death in the IPA-risk subgroup only, with hazard ratio (HR): 3.687 (95% confidence interval CI, 1.030-13.199, P = 0.045) for the diagnosis of probable CAPA, and HR: 1.022 (95% CI, 1.003-1.042, P = 0.026) for every 1 ng/mL rise in PCT.
CONCLUSIONS: Patients in the IPA-risk subgroup that were diagnosed with CAPA had a lower 90-day survival when compared to patients in the same group without a CAPA diagnosis.
COVID-19 might present with a wide range of clinical manifestations, from mild respiratory distress to severe multi-organ dysfunction. We present a unique case of complex COVID-19 presentation in a ...45-year-old female who initially developed general symptoms such as fever, cough, headache, and weakness, which escalated to coma, requiring intubation and ICU admission. A brain MRI revealed lesions compatible with encephalitis, the cause of which remained unexplained after an in-depth clinical, laboratory, and imaging investigation. While in the ICU, the patient also developed cardiac tamponade, requiring pericardiocentesis, and atypical electrocardiographic changes. After treatment with steroids, her condition improved, and the patient was extubated and transferred to the ward. Upon checkup, cardiac MRI revealed fibrous tissue in the inferior cardiac wall and the adjacent intraventricular septum. In the absence of an alternative diagnosis, it might be important to consider the central nervous system and cardiac involvement in patients with COVID-19.
Studies have supported the correlation between mean platelet volume and COPD. However, there are limited data on the relationship between COPD exacerbation and mean platelet volume. We aimed to ...evaluate the mean platelet volume trend in patients with COPD exacerbation.
A total of 81 subjects, 62 men and 19 women, who were admitted to the hospital because of exacerbation of COPD during 9 months, were enrolled in this prospective observational study. The levels of mean platelet volume, C-reactive protein, complete blood count, and percent-of-predicted FEV1 were measured in subjects at admission (exacerbation period) and after 3 months (stable period). Thirty-seven age- and sex-matched healthy individuals constituted the control group.
Subjects in the exacerbation period had significantly higher levels of C-reactive protein (P = .001), white blood cell count (P = .01), and percentage of neutrophils (P = .01) and lower percent-of-predicted FEV1 than in the stable period (P = .02). Mean platelet volume levels were significantly decreased in the exacerbation period (P = .001). Considering a cut-off point of mean platelet volume levels <8.2 fL for indicating COPD exacerbation showed a sensitivity of 80% and a specificity of 76%. Also, mean platelet volume levels correlated significantly with increase of C-reactive protein level, white blood cell count, and neutrophil percentage in the exacerbation period (P = .01, P = .01, and P = .02, respectively).
Mean platelet volume may be an inflammatory marker in exacerbation of COPD, and the measurement of mean platelet volume values may be useful for identifying patients who are at increased risk for exacerbations of illness.
Fenofibrate is widely prescribed as a hypolipidemic drug and is well tolerated by most patients. We present the case of a 40-year-old woman who developed severe immune thrombocytopenia while on ...fenofibrate treatment. Clinical features included spontaneous bruising on the feet and hands, a purpuric rash, and menorrhagia. All the laboratory results were normal except for the finding of isolated thrombocytopenia. The subsequent evolution was favorable after fenofibrate removal and with the administration of immunoglobulin G (IgG) plus corticosteroids. Drug-induced thrombocytopenia is briefly reviewed, and a possible mechanism responsible for causing this side effect of fenofibrate is suggested. This is the first reported case of fenofibrate-induced immune thrombocytopenia.
ABSTRACT
Background and objective: There are limited data on the relationship between the severity of community‐acquired pneumonia (CAP) and biomarkers of inflammation and coagulation. The aim of ...this study was to evaluate the association between the severity of CAP and serum levels of antithrombin III (AT‐III), protein C (P‐C), D‐dimers (D‐D) and CRP, at hospital admission.
Methods: This was a prospective observational study in 77 adults (62.3% men), who were hospitalized for CAP. The severity of CAP was assessed using the confusion, uraemia, respiratory rate ≥30 breaths/min, low blood pressure, age ≥65 years (CURB‐65) score.
Results: Forty patients (52%) had severe CAP (CURB‐65 score 3–5). Serum levels of AT‐III were lower and levels of D‐D and CRP were higher in patients with severe CAP than in patients with mild CAP (CURB‐65 score 0–2) (P < 0.001 for all comparisons). Levels of P‐C were lower in patients with severe CAP compared with those with mild CAP, but the difference was not significant (P = 0.459). At a cut‐off point of 85%, AT‐III showed a sensitivity of 80% and a specificity of 75%, as a determinant of the need for hospitalization. At a cut‐off point of 600 ng/mL, D‐D showed a sensitivity of 90% and a specificity of 75% and at a cut‐off point of 110 mg/L, CRP showed a sensitivity of 83% and a specificity of 79%, as determinants of the need for hospitalization.
Conclusions: Serum levels of AT‐III, D‐D and CRP at admission appear to be useful biomarkers for assessing the severity of CAP.
The role of inflammation and coagulation biomarkers in predicting the severity of community‐acquired pneumonia (CAP) was assessed. Serum levels of antithrombin‐III, protein‐C, D‐dimers and CRP at admission appear to be useful biomarkers for assessing the severity of CAP.
Abstract Candida auris is an emerging fungal pathogen associated with multi-drug resistance rates and widespread outbreaks in hospitals and healthcare units worldwide. Sequencing studies have ...revealed that different clonal lineages of the fungus seem to be prevalent among distinct geographical sites. The first case of C. auris in Northern Greece was reported in Thessaloniki in October 2022, almost 2 years after the first isolation in Greece (Athens 2019). The Mycology Laboratory of the Medical School of Aristotle University of Thessaloniki stands as the reference laboratory for fungal diseases in Northern Greece and a meticulous search for the yeast, in plenty of suspicious samples, has been run since 2019 in the Lab as well as a retrospective analysis of all its yeasts’ collection, back to 2008, with negative results for the presence of C. auris. Here, are presented the findings concerning the outbreak and surveillance of C. auris in Northern Greece, mainly the region of Thessaloniki and the broader area of Macedonia, from October 2022 until August 2023. The isolates from Northern Greece continue to fall in Clade I and present with an almost equal and stable sensitivity profile until now.
Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and ...outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation.
WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109.
Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital.
In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates.
European Society of Intensive Care Medicine, European Respiratory Society.
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