Smart Capsule For Targeted Detection Of Inflammation Levels Inside The Gi Tract.

Effective management of Inflammatory Bowel Disease (IBD) is contingent upon frequent monitoring of inflammation levels at targeted locations within the gastrointestinal (GI) tract. This is crucial for assessing disease progression and detecting potential relapses. To address this need, a novel single-use capsule technology has been devised that enables region-specific inflammation measurement, thereby facilitating repeatable monitoring within the GI tract. The capsule integrates a pH-responsive coating for location-specific activation, a chemiluminescent paper-based myeloperoxidase (MPO) sensor for inflammation detection, and a miniaturized photodetector, complemented by embedded electronics for real-time wireless data transmission. Demonstrating linear sensitivity within the physiological MPO concentration range, the sensor is capable of effectively identifying inflammation risk in the GI fluid. Luminescence emitted by the sensor, proportional to MPO concentration, is converted into an electrical signal by the photodetector, generating a quantifiable energy output with a sensitivity of 6.14 µJ/U.ml-1. The capsule was also tested with GI fluids collected from pig models simulating various inflammation states. Despite the physiological complexities, the capsule consistently activated in the intended region and accurately detected MPO levels with less than a 5% variation between readings in GI fluid and a PBS solution. This study heralds a significant step towards minimally invasive, in situ GI inflammation monitoring, potentially revolutionizing personalized IBD management and patient-specific therapeutic strategies.

Smart capsule for monitoring inflammation profile throughout the gastrointestinal tract.

Inflammatory bowel disease (IBD) has become alarmingly prevalent in the last two decades affecting 6.8 million people worldwide with a starkly high relapse rate of 40% within 1 year of remission. Existing visual endoscopy techniques rely on subjective assessment of images that are error-prone and insufficient indicators of early-stage IBD, rendering them unsuitable for frequent and quantitative monitoring of gastrointestinal health necessary for detecting regular relapses in IBD patients. To address these limitations, we have implemented a miniaturized smart capsule (2.2 cm × 11 mm) that allows monitoring reactive oxygen species (ROS) levels as a biomarker of inflammation for quantitative and frequent profiling of inflammatory lesions throughout the gastrointestinal tract. The capsule is composed of a pH and oxidation reduction potential (ORP) sensor to track the capsule's location and ROS levels throughout the gastrointestinal tract, respectively, and an optimized electronic interface for wireless sensing and data communication. The designed sensors provided a linear and stable performance within the physiologically relevant range of the GI tract (pH: 1-8 and ORP: -500 to +500 mV). Additionally, systematic design optimization of the wireless interface electronics offered an efficient sampling rate of 10 ms for long-running measurements up to 48 h for a complete evaluation of the entire gastrointestinal tract. As a proof-of-concept, the capsule the capsule's performance in detecting inflammation risks was validated by conducting tests on in vitro cell culture conditions, simulating healthy and inflamed gut-like environments. The capsule presented here achieves a new milestone in addressing the emerging need for smart ingestible electronics for better diagnosis and treatment of digestive diseases.

SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity.

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Helicobacter pylori antimicrobial resistance in Melbourne, Australia. Time to review therapeutic guidelines?

BACKGROUND: Antimicrobial resistance (AMR) in Helicobacter pylori is a global concern. The AMR data to inform the Australian Therapeutic Guidelines are based on data over 20 years old. AIMS: To evaluate the frequency of AMR in H. pylori isolates from gastric biopsy specimens received in our laboratory in Melbourne, Australia. To review the literature on resistance rates in Australia and compare historic data. METHODS: A retrospective, observational study summarising AMR rates in all H. pylori isolates from our laboratory from 2015 to June 2020. Microbiology laboratory in metropolitan Melbourne, Australia, receiving referrals from private hospitals, gastroenterology clinics and endoscopy suites. Population minimum inhibitory concentration distributions and frequency of resistance to clarithromycin, amoxicillin, metronidazole and tetracycline in H. pylori isolates. RESULTS: Three hundred and eighty-six H. pylori isolates with susceptibility testing data were identified. The frequency of resistance in this cohort was: clarithromycin 89.9%, amoxicillin 23.5%, metronidazole 66.1% and tetracycline 4.4%. Comparison with historical data may suggest increasing AMR rates in Australia. The main limitation is the lack of treatment history to correlate AMR results. CONCLUSIONS: Definitive conclusions from this cohort cannot be made, but trends suggest rising levels of primary H. pylori AMR rates in Australia. This has important implications for empirical treatment decision making and treatment outcomes. Primary H. pylori AMR requires dedicated studies and current Australian therapeutic guideline recommendations may require re-evaluation. We propose considerations for improving the management of H. pylori in Australia. A centralised public health approach to H. pylori AMR surveillance should be established.

An evaluation of 4 commercial assays for the detection of SARS-CoV-2 antibodies in a predominantly mildly symptomatic low prevalence Australian population.

A total of 1080 individual patient samples (158 positive serology samples from confirmed, predominantly mildly symptomatic COVID-19 patients and 922 serology negative including 496 collected pre-COVID) from four states in Australia were analysed on four commercial SARS-CoV-2 serological assays targeting antibodies to different antigens (Roche Elecsys and Abbott Architect: nucleocapsid; Diasorin Liaison and Euroimmun: spike). A subset was compared to immunofluorescent antibody (IFA) and micro-neutralisation. Sensitivity and specificity of the Roche (n = 1033), Abbott (n = 806), Diasorin (n = 1034) and Euroimmun (n = 175) were 93.7 %/99.5 %, 90.2 %/99.4 %, 88.6 %/98.6 % and 91.3 %/98.8 %, respectively. ROC analysis with specificity held at 99 % increased the sensitivity for the Roche and Abbott assays from 93.7% to 98.7% (cut-off 0.21) and 90.2 % to 94.0 % (cut-off 0.91), respectively. Overall seropositivity of samples increased from a maximum of 23 % for samples 0-7 days-post-onset of symptoms (dpos), to 61 % from samples 8-14dpos and 93 % from those >14dpos. IFA and microneutralisation values correlated best with assays targeting antibodies to spike protein with values >80 AU/mL on the Diasorin assay associated with neutralising antibody. Detectable antibody was present in 22/23 (96 %), 20/23 (87 %), 15/23 (65 %) and 9/22 (41 %) patients with samples >180dpos on the Roche, Diasorin, Abbott and microneutralisation assays respectively. Given the low prevalence in this community, two-step algorithms on initial positive results saw an increase in the positive predictive value (PPV) of positive samples (39 %-65 % to ≥98 %) for all combinations. Similarly accuracy increased from a range of 98.5 %-99.4 % to ≥99.8 % assuming a 1 % seroprevalence. Negative predictive value (NPV) was high (≥99.8 %) regardless of which assay was used initially.

Very late-onset cytomegalovirus disease with ganciclovir resistance >15 years following renal transplantation.

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality after solid organ transplantation. There has been a significant shift in disease epidemiology with the introduction of antiviral prophylaxis, with CMV disease occurring later and clinical presentations more atypical. We describe two cases of very late-onset CMV disease where first disease occurred 15 and 18 years post-renal transplantation, with both cases complicated by antiviral drug resistance. We subsequently review the published cases and literature of very late-onset CMV disease (onset > 10 years post-solid organ transplantation) as an increasingly recognized phenomenon which is emerging as an important aspect in improving long-term patient outcomes in the current era of renal transplantation.

Treatment of invasive IMP-4 Enterobacter cloacae infection in transplant recipients using ceftazidime/avibactam with aztreonam: A case series and literature review.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo-ß-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer ß-lactamase inhibitors such as avibactam have well-established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL-producing organisms. Conversely, aztreonam has activity against MBL-producing organisms but is often inactivated by other co-existing ß-lactamases. Here, we report four cases of invasive MBL-CPE infections in transplant recipients caused by IMP-4-producing Enterobacter cloacae who were successfully treated with a new, mechanism-driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high-risk patients with CPE infection, with reduced drug interactions and toxicity.

When Ventricular Cerebrospinal Fluid Assessment Misleads: Basal Meningitis and the Importance of Lumbar Puncture Sampling.

The diagnosis of central nervous system (CNS) infection relies upon analysis of cerebrospinal fluid (CSF). We present 4 cases of CNS infections associated with basal meningitis and hydrocephalus with normal ventricular CSF but grossly abnormal lumbar CSF. We discuss CSF ventricular-lumbar composition gradients and putative pathophysiological mechanisms and highlight clinical clues for clinicians.

Mycobacterium abscessus bloodstream infection: Unexpected catheter tunnel infection localized by PET/CT.

Mycobacterium abscessus is an emerging cause of invasive infection in the immunosuppressed population. We report a case of M. abscessus bloodstream and catheter tunnel infection localized by positron emission tomography/computer tomography (PET/CT) in an allogeneic haematopoietic stem cell transplant recipient. This case highlights the difficulties in treating invasive M. abscessus infection and the potential role of PET/CT in localizing infection and guiding therapy in this population.