Temporal association between antibiotic use and resistance in Gram-negative bacteria

The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Case report of acute myocarditis after administration of COVID-19 vaccine in Japan

Background The worldwide spread of Coronavirus disease 2019 (COVID-19) is still not under control and vaccination in Japan started in February 2021, albeit later than in Europe and the United States of America. The COVID-19 vaccination frequently leads to minor adverse reactions, that may be more intense after the second dose. The number of case reports of myocarditis following COVID-19 vaccination have been recently increased. Case Summary We report a case of a 26-year-old healthy man who presented to our hospital with chest pain on May 24 2021, 4 days after his second COVID-19 vaccination. The electrocardiogram showed ST elevation with upward concavity in I, II, aVL, aVF, V4 to V6, and small Q wave in II, III, aVF. Laboratory studies revealed elevation of troponin-I, creatine kinase, C-reactive protein and negative viral serologies. Acute aortic dissection and pulmonary thromboembolism were ruled out by contrast-enhanced thoracoabdominal computed tomography (CT). An urgent coronary angiogram was performed because an acute coronary syndrome was suspected, but no significant stenosis was found. Cardiac magnetic resonance imaging (MRI) demonstrated oedema and late gadolinium enhancement of the left ventricle in a midmyocardial and epicardial distribution. Discussion Although the temporal association does not prove causation, the very short span between the second vaccination and the onset of myocarditis suggests that this acute myocarditis seemed to be an adverse reaction to COVID-19 vaccine. To the best of our knowledge, this is the first published case of acute myocarditis following COVID-19 vaccine in Asia.

Ocular inflammatory events following COVID-19 vaccination: a multinational case series

Background Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine’s immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. Methods Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. Results Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19–84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1–14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). Conclusion Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome.

Post-Hematopoietic Stem Cell Transplantation Immune-Mediated Anemia: A Literature Review and Novel Therapeutics

Anemia following allogeneic hematopoietic stem cell transplantation (HCT) can be immune- or non-immune mediated. Auto- or alloimmunity due to blood groups incompatibility remain an important cause if post-HCT immune-mediated anemia. ABO incompatibility is commonly encountered in HCT and may lead to serious clinical complications including acute hemolysis, pure red cell aplasia, and passenger lymphocyte syndrome. It remains controversial whether ABO incompatibility may affect HCT outcomes, such as relapse, non-relapse mortality, graft-versus-host disease and survival. Non-ABO incompatibility is less frequently encounterd but can have similar complications to ABO incompatibility, causing adverse clinical outcomes. It is crucial to identify the driving etiology of post-HCT anemia in order to prevent and treat this condition. This requires a comprehensive understanding of the mechanism of anemia in blood group incompatible HCT, and the temporal association between HCT and anemia. In this review, we summarized the literature on post-HCT immune-mediated anemia with a focus on ABO and non-ABO blood group incompatibility, described the underlying mechanism of anemia, and outlined preventive and treatment approaches.

Leukocytoclastic Vasculitis Following COVID-19 Vaccination: A Case Report

Background: Hypersensitivity or Leukocytoclastic vasculitis (LCV) following the COVID-19 vaccination has been reported rarely all over the world. LCV can be induced by certain factors such as infections, autoimmune disorders, malignancy, or some classes of drugs. Case presentation: A 32-year-old man, who was a known case of seizure disorder from his childhood presented to the department of dermatology with itchy red lesions on extremities and abdomen for the past 1 month. He explains a history of COVID-19 vaccination 1-month back and experienced itching on his lower limbs on the same day at night. A gradual worsening of the condition was observed day by day. He was hospitalized and diagnosed as LCV through clinical and laboratory findings. Conclusion: This case highlights a temporal association with the event of vaccination. The causality assessment showed an indeterminate causal association to LCV with COVID-19 Vaccination.

Is COVID-19 multisystem inflammatory syndrome a new variant of Kawasaki Disease?

Objectives: In this systematic review, we aimed to evaluate the clinical features, therapeutic options, and outcomes of children with multisystem inflammatory syndrome in children (MIS-C) and to investigate whether MIS-C is a new variant of Kawasaki disease. Materials and methods: Adhering to PRISMA principles, we searched for eligible studies between December 2019 and June 2020 through the following databases: PubMed, ISI Web of Science, SCOPUS, and Science Direct. Studies including original data of patients aged <21 years with MIS-C and descriptions of clinical signs, laboratory or radiological investigations were selected. Results: A total of 84 studies were identified, for which 48 were eligible for full screening and only 13 studies (n=657) met our inclusion criteria. More than 70% of patients with MIS-C tested positive for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The most common symptoms were gastrointestinal (80 to 100%) and most patients presented with fever for >4 days. Mucocutaneous manifestations are similar to Kawasaki disease presented in up to 64% in some studies. Almost all patients had significant elevations in inflammatory markers, and up to 50 to 100% had elevated troponin suggesting myocardial damage. Intravenous immunoglobulin (IVIG) was administered to 60% of patients in 12 studies and 80 to 100% in five studies. Steroids were administered to 10 to 95% of patients. The overall mortality rate was 0.9%. Conclusion: The temporal association between novel coronavirus disease 2019 (COVID-19) onset and Kawasaki-like disease and MIS-C suggests a causal link. Both syndromes have similar cascades of symptoms and hyperinflammation, which likely explain their response to the same immunomodulatory agents. However, it is unclear yet why some children appear more susceptible to develop MIS-C.

Exacerbation of Psoriasis Following COVID-19 Vaccination: Report From a Single Center

The temporal association had been reported between vaccination and exacerbation of psoriasis, and episodes of psoriasis flare-up have recently been attributed to COVID-19 vaccines. We recruited 32 unimmunized controls and 51 vaccinated psoriasis patients, 49 of whom were under biological therapy, with regular clinic visits receiving a total of 63 shots of vaccines, including 30 doses of Moderna mRNA-1273 and 33 doses of AstraZeneca-Oxford AZD1222. Fifteen episodes of exacerbation attacked within 9.3 ± 4.3 days, which is higher than two episodes in the control group (p = 0.047). The mean post-vaccination severity of the worsening episodes increased from PASI 3.1 to 8.0 (p &lt; 0.001). Three patients showed morphologic change from chronic plaque-type to guttate psoriasis. Deterioration of psoriasis following COVID-19 vaccination was not associated with age, sex, disease duration, psoriatic arthritis, family history of psoriasis, history of erythroderma, current biologics use, comorbidities, vaccine types, human leukocyte antigen (HLA)-C genotypes, baseline PASI nor pre-vaccination PASI. For those who received two doses of vaccination, all but one patient aggravated after the first shot but not the second. The mechanism of psoriasis exacerbation in immunized individuals is unclear, but Th17 cells induced by COVID-19 vaccines may play a role. In the pandemic era, psoriasis patients and physicians should acknowledge the possibility of fluctuation of disease activity when vaccinated against COVID-19. Nevertheless, compared to a treatable dermatologic disease with rapid resolution of exacerbation, psoriasis patients who do not have contraindications to vaccination should benefit from COVID-19 vaccines in the prevention of severe COVID-19 infection and fatality.

Role of sediment in generating contemporaneous, diverse “type” granitoid magmas

Granite typology categorizes granitoid rocks based upon distinguishing characteristics that are interpreted to indicate sources, conditions of generation, and, by implication, tectonic setting. Complexities of elemental and isotopic geochemistry, however, commonly preclude simple typological interpretation and suggest more complex petrogenetic histories. Granitoids from the Songpan-Ganzi terrane in the eastern Tibetan Plateau were emplaced within a short interval (~15 m.y.). They display mineralogical and geochemical characteristics that are consistent with a wide range of proposed typologies (I-, S-, and A-type; high Ba-Sr and adakitic variants). Despite their close spatial and temporal association, these granitoids exhibit diversity in geochemical characteristics that indicates a broad spectrum of contributing sources. Radiogenic isotope data reveal a continuum from primitive to evolved crustal compositions; i.e., 87Sr/86Sr(t) = 0.704–0.715 and εNd(t) = +2 to –11. All granitoid “types” have variable but commonly high zircon δ18O (+4.1‰ to +11.6‰) and low whole-rock Li-B-Mg isotopic ratios compared to mantle and/or seawater (δ7Li = +5.1‰ to –3.2‰; δ11B = –10.7‰ to –16.5‰; δ26Mg = –0.23‰ to –0.59‰). These stable isotopic compositions suggest that the Songpan-Ganzi granitic magmas of all “types” had contributions from sediment, ranging from minor to dominant. The highly variable isotopic compositions of the granitoids rule out a single homogeneous source for these diverse yet contemporaneous granitoids. Their compositional variability may have been significantly influenced by sedimentary contributions, and these results demonstrate the difficulty of straightforward assignment and interpretation of granitoids using conventional typology.

Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease

Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.