Interpretation,pitfalls of biomarkers in diagnosis of invasive fungal diseases

BackgroundInvasive Fungal Diseases (IFD), account for high morbidity and mortality in immunocompromised and seriously ill patients worldwide. Early, faster and accurate diagnosis with timely and appropriate patient management is critical for improved patient outcome and antifungal stewardship. Clinical/radiological presentations in IFD are non-specific and microscopy/culture based tests have low sensitivity and long turnaround time. Biomarkers have clinical utility for diagnosing IFD but their interpretation is not straight forward.ObjectivesThis review discusses the salient characteristics, clinical usefulness and limitations of common biomarkers such as Galactomannan (GM), 1–3, β D glucan (βDG), mannan, anti-mannan antibody (Mn/antiMn), Cryptococcal antigen test (CrAg), Nucleic Acid Amplification (NAA) tests and next generation sequencing for diagnosing IFD.ContentsFungal biomarkers are useful adjuncts as screening and diagnostic tools for IFD and are much more suited for ‘ruling out’ rather than ‘ruling in’ disease. GM, NAA tests are promising biomarkers for screening of invasive Aspergillosis in high risk asymptomatic patients who are not on antifungal therapy and for diagnosis of breakthrough infections in symptomatic patients. 1–3, β D glucan has limitations both as a ‘rule in’ and ‘rule out’ test and is useful in only specific clinical settings. Two consecutive positive 1-3-βDG tests or combined positivity with GM increases its specificity. Mn/antiMn, T2Candida nano diagnostic panel are promising candidates for diagnosing invasive candidiasis. Combining two or more biomarkers improves the sensitivity for prompt initiation of antifungal therapy and the negative predictive value for suspension of empirical treatment.Serum CrAg test is a good ‘rule in’ rather than a ‘rule out’ test in immunocompetent patients but has good diagnostic accuracy in immunocompromised patients. Detection of single nucleotide polymorphisms by next generation sequencing is useful for fungal characterization and identification of host determinants responsible for increased susceptibility to fungal infections but is still in experimental stages.     

Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.     

Preoperative tendon retraction,not smoking,is a risk factor for failure with continuity after rotator cuff repair

BackgroundSmoking is a poor prognostic factor for healing after rotator cuff repair and is associated with inferior results. We hypothesized that smokers would have higher recurrent tear rates and more postoperative myotendinous junction (MTJ) retraction in healed repairs than nonsmokers three months postoperatively.MethodsRotator cuff repairs (RCRs) were retrospectively reviewed over a 2-year period. Patients underwent magnetic resonance imaging (MRI) within 6 months prior to surgery and again at 3 months postoperatively. Seventy-nine patients were included and stratified by smokers versus nonsmokers. Baseline patient demographics, tear characteristics, and surgical factors were collected. Preoperative and postoperative MRIs were assessed to quantify the MTJ position and to establish the recurrent tear rate.ResultsFor the total cohort (nonsmokers, n = 56; smokers, n = 23), significant differences in age, race, and traumatic onset of injury existed between groups. There were no significant differences in recurrent tear between smokers (26%) and nonsmokers (27%), but nonsmokers were more satisfied. For patients with healed RCRs (nonsmokers, n = 41; smokers, n = 17), there were significant differences in race. On univariate analysis, nonsmokers had a significantly more lateral MTJ postoperatively (P = 0.05). On multivariable regression analysis, medialized postoperative MTJ position in healed cuffs was driven only by greater preoperative rotator cuff retraction preoperatively. There were no significant differences in MTJ position based on smoking status for patients with healed RCRs.ConclusionSmoking does not appear to be an independent risk factor for postoperative MTJ retraction in healed RCRs, also known as failure in continuity. Preoperative tear size and retraction play the biggest roles in predicting postoperative MTJ position, regardless of smoking status. There are no significant differences in patient-reported outcomes for patients with healed RCRs, but nonsmokers had more satisfaction following RCR in the total cohort.Level of EvidenceLevel III; Retrospective cohort study; Diagnostic study