Late Reactions Research Articles

Letermovir Discontinuation at Day 100 After Allogeneic Stem Cell Transplant Is Associated With Increased CMV-Related Mortality

Letermovir is approved by the Food and Drug Administration for cytomegalovirus (CMV) prophylaxis in CMV seropositive recipients of allogeneic stem cell transplantation (alloSCT) up to day 100. Letermovir use up to day 100 after alloSCT has demonstrated a significantly lower incidence of clinically significant CMV infection (csCMVi) at 24 weeks and an overall mortality benefit as far as 48 weeks after transplantation. We report data on csCMVi incidence beyond 24 weeks and overall survival (OS) beyond 48 weeks and outcomes for patients who had a prior alloSCT, are CMV seronegative with seropositive donor (D+/R−), or are high risk (defined as those receiving haploidentical transplants, mismatched transplants, T-cell–depleted grafts, umbilical cord blood transplants, prednisone ≥1 mg/kg or equivalent steroid use, or the use of 2 or more immunosuppressants). Additionally, risk factors for CMV-related mortality and possible extended duration of letermovir are reported. This is a single-center, retrospective cohort study of 333 alloSCTs with CMV seropositive donors or recipients performed at Siteman Cancer Center and Barnes-Jewish Hospital from January 2016 to June 2019. The primary endpoint of csCMVi at day 180 was 19.46% with letermovir and 39.13% without letermovir (P < .0001). The secondary endpoints are as follows: day 100 csCMVi was 8.1% with letermovir and 34.8% without (P < .0001), day 365 csCMVi was 24.8% with letermovir and 41.3% without (P = .001). Our multivariate analyses demonstrated that exposure to letermovir was associated with improved OS (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.25-0.77), nonrelapse mortality (HR 0.50; 95% CI 0.27-0.94) and CMV-related mortality (HR 0.40; 95% CI 0.16-0.95) during day 0 to day 99 but worse CMV-related mortality during day 180 to day 364 (HR 3.19; 95% CI 1.29-7.92). Patients with serum IgG levels <400 mg/dL at day 100, high-risk transplants (P = .004), post-transplantation cyclophosphamide (PTCy; P = .001), and mismatched-unrelated donors (MMUD; P = .02) experienced increased CMV reactivation. The CMV D+/R− cohort demonstrated no difference in CMV reactivation overall (P = .19), but the subset receiving PTCy showed decreased reactivation with letermovir (P = .03). Discontinuation of letermovir at day 100 leads to increased incidence of late CMV reactivation and CMV-related mortality. Letermovir use in CMV recipient seropositive alloSCT may need to be extended. Serum IgG levels <400 mg/dL at day 100 was associated with increased CMV reactivation. Patients with subclinical CMV viremia before transplantation, high-risk transplants, PTCy, or MMUD had decreased CMV reactivation with letermovir. Although there was no difference in CMV reactivation in the CMV D+/R− cohort, the subset treated with PTCy for acute graft-versus-host disease prophylaxis had decreased CMV reactivation with letermovir.

Deep and surface driving forces that shape the Earth: Insights from the evolution of the northern South China sea margin

The sediments and their temporal and spatial distribution on Earth are the archives of interaction between deep and surface processes. Numerous simulations have attempted to decipher the evolution of landscape and sedimentary basins. However, it remains a challenge to couple paleogeographic evolution with deep geodynamics, especially at the continental margins such as the Northern South China Sea Margin (NSCSM). Here we employ a numerical simulating tool (Badlands) for the tectono-sedimentary evolution of the NSCSM to test and compare our restored interpolated paleo-bathymetries with previously published paleogeography. Based on the subsequent reconstruction of cumulative sediment thicknesses at the distal boundary of the continental margin, we found that the erodibility and elastic thickness of the lithosphere are the best-fitted and the most promising parameters to isostatically deal with deep dynamics in controlling regional topography. According to our findings, the Early Oligocene and Early Miocene are two stages of high erodibility and fast uplifting in the source provenances or weathering regions as well as lithospheric strengthening. In contrast, the lower values of elastic thickness indicate the Eocene rifting and Late Miocene reactivation of extension due to its lithospheric weakening, relative to the post-rift thickening.Plain language summary: Transient deep and surface processes actively participated in the geography of Earth’s landscape and sediment distribution. It takes millions of years for these processes and remains challenging to investigate the past landscape evolution. However, in the era of numerical modelling and more advanced research, it is now possible to solve many scientific questions. This study also attempted to find paleogeographic core findings based on the combined effect of deep and surface processes using a numerical simulation tool, Badland. Finally, we establish an erosion as a surface leading factor and an elastic thickness of lithosphere and mantle convection as the deep dynamic factors, to effect the Earth’s surface landscape and link with the accumulation of sediments.

High-dose-rate brachytherapy as monotherapy for prostate cancer: 5-year results

Objective: to evaluate clinical outcomes in patients with prostate cancer treated with high-dose-rate (HDR) brachytherapy (BT) as monotherapy.Materials and methods. From January 2015 to December 2017, 97 men with localized prostate cancer underwent HDR-BT as monotherapy, with a temporary implant on a MicroSelectron HDR device. The dose prescription was: 30 Gy in 2 fractions with an interval of 2 weeks. The overall and biochemical survival rate was assessed. The assessment of genitourinary and gastrointestinal toxicity was also carried out. The quality of life associated with urination before treatment and in dynamics during 5 years of observation, as well as the frequency and degree of development of erectile dysfunctionand its dynamics during the entire observation period were analyzed.Results. The median age was 65.2 (44 to 80) years. Overall, 29 patients had low risk prostate cancer, 63 patients had moderate risk, and 5 patients – high risk. The follow-up period was five years (range, 18 to 72 months). The median follow-up was 54.3 (95 % confidence interval 52.3–59) months. Overall survival and survival without biochemical recurrence were 96 and 99 %, respectively. Toxicity was assessed according to the RTOG/EORTC (Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer) scale for each event. Late genitourinary toxic reactions of grade 1 and 2 were noted in 23.9 and 6.3 %, respectively. Late gastrointestinal grade 2 toxicity was not observed. Genitourinary and gastrointestinal toxic reactions of grade 3 were not observed. The quality of life associated with urination after treatment was comparable to the level of quality of life at the time of inclusion of patients in the treatment protocol. Erectile dysfunction developed to a greater extentin the first 1–2 years after HDR-BT with a subsequenttendency to recovery.Conclusion. HDR-BT as monotherapy is a safe and highly effective treatment for localized prostate cancer. The fractionation mode in the form of 30 Gy for 2 fractions of 15 Gy with an interval of 2 weeks with or without dose modulation in the area of the tumor focus using a gel has a low toxicity profile from the side of critical organs.

Cysteinyl–leukotriene and prostaglandin pathways in bronchial versus alveolar lavage in allergic asthmatics

Cysteinyl–leukotriene and prostaglandin pathways in bronchial versus alveolar lavage in allergic asthmatics

Neutrophil phenotypes in bronchial airways differentiate single from dual responding allergic asthmatics.

Allergic asthmatics with both an early (EAR) and a late allergic reaction (LAR) following allergen exposure are termed 'dual responders' (DR), while 'single responders' (SR) only have an EAR. Mechanisms that differentiate DR from SR are largely unknown, particularly regarding the role and phenotypes of neutrophils. Therefore, we aimed to study neutrophils in DR and SR asthmatics. Thirty-four allergic asthmatics underwent an inhaled allergen challenge, samples were collected before and up to 24h post-challenge. Cell differentials were counted from bronchial lavage, alveolar lavage and blood; and tissue neutrophils were quantified in immune-stained bronchial biopsies. Lavage neutrophil nuclei lobe segmentation was used to classify active (1-4lobes) from suppressive neutrophils (≥5lobes). Levels of transmigration markers: soluble (s)CD62L and interleukin-1Ra, and activity markers: neutrophil elastase (NE), DNA-histone complex and dsDNA were measured in lavage fluid and plasma. Compared with SR at baseline, DR had more neutrophils in their bronchial airways at baseline, both in the lavage (p=.0031) and biopsies (p=.026) and elevated bronchial neutrophils correlated with less antitransmigratory IL-1Ra levels (r=-0.64). DR airways had less suppressive neutrophils and more 3-lobed (active) neutrophils (p=.029) that correlated with more bronchial lavage histone (p=.020) and more plasma NE (p=.0016). Post-challenge, DR released neutrophil extracellular trap factors in the blood earlier and had less pro-transmigratory sCD62L during the late phase (p=.0076) than in SR. DR have a more active airway neutrophil phenotype at baseline and a distinct neutrophil response to allergen challenge that may contribute to the development of an LAR. Therefore, neutrophil activity should be considered during targeted diagnosis and bio-therapeutic development for DR.

Too Late Allergic Reaction in Patient with Permanent Pacemaker

Contact allergy to cardiac implantable electronic devices is a rare problem in patients. Clinical evaluation and patch tests have an important place in its diagnosis. Also in this case, the diagnosis is supported by ultrasonography. It has been reported in the literature that allergic dermatitis developed after permanent pacemaker implantation in the first few days until the current year. In our case report, we showed that the allergic reaction in the patient was too late. In this article, we present a 94-year-old male patient with a permanent pacemaker who came to us with the complaint of redness and itching in the left chest area and was diagnosed with contact allergy.

Randomized controlled trial of colchicine add on to the standard therapy in moderate and severe corona virus Disease-19 infection

BackgroundCOVID19 complications cause inflammatory storm. Colchicine is a potent anti-inflammatory medication that has been proposed as a possible treatment option for COVID-19. Objectiveto assess effectiveness and safety of add on use of colchicine to the standard treatment in moderate and severe COVID-19. Patients and methodsIn this randomized controlled open label clinical trial, 160 patients hospitalized equally divided between moderate and severe COVID19 categories were randomized to 4 study groups in a 1:1:1:1 allocation (n = 40 for each group) according to type of treatment. Patients were randomly assigned to receive the standard treatment for 14 days (control group) or colchicine add on to the standard treatment 1 mg daily orally for 7 days then 0.5 mg daily for another 7 days. Survival rate, time to cure in days, and side effects were assessed. ResultsColchicine add on treatment was associated with a significantly shorter time to cure (referring to start of first symptom) by an average of 5 days in severe disease and 2 days in moderate disease (log-rank P=<0.001). In addition, the Colchicine add on significantly increased the risk of cure per unit of time by 2.69 times compared to controls after adjusting for disease severity, age, and time since the start of the disease to start of treatment. A severe COVID19 disease, a longer time for starting treatment, and the older age notably reduced the risk of cure (HR = 0.72, p = 0.07; HR = 0.74, p < 0.001; and HR = 0.59, p = 0.015 respectively). Possible side effects reported due to colchicine were 8/40 (20%) of severe COVID19 patients and 3/40 (7.5%) of moderate COVID19, non of which warranted stopping treatment by the data monitoring board. Generally, the side effects were 8/11 (72.73%) gastrointestinal disturbances. No immediate or late allergic reactions were observed. ConclusionsColchicine add on treatment reduced significantly time to recovery in severe COVID19 (by five days) and in moderate cases (by two days) but did not lower the death rate. Side effects were mild, well tolerated and confined to gastrointestinal adverse events.

Microarray Analysis Confirms ImmunoCAP-Fluorescence Enzyme Immunoassay Results on Specific IgE in Patients with Atopic Dermatitis and Suspected Birch Pollen-Related Food Allergy

Background: Previous studies demonstrated that birch pollen-related foods can cause late eczematous responses in birch pollen-sensitized patients with atopic dermatitis (AD). However, suitable markers to predict birch pollen-related food allergy in patients with AD are still lacking. Objective: We evaluated the correlation of the results from ImmunoCAP® fluorescence enzyme immunoassay (FEIA) singleplex and ImmunoCAP® immuno solid-phase allergen chip (ISAC) multiplex system in AD patients and investigated the diagnostic validity of allergen microarray analysis, measuring specific IgE (sIgE) with ImmunoCAP® ISAC to predict birch pollen-related food allergy in patients with AD. Methods: A total of 19 children and adults with AD, existing IgE-mediated birch pollen sensitization, and suspected birch pollen-related food allergy underwent a double-blind placebo-controlled food challenge (DBPCFC) in the clinical routine. Total and sIgE levels to birch pollen, Bet v 1, Bet v 2, and birch pollen-related foods (apple, carrot, celery, and hazelnut) were determined prior to the DBPCFC by ImmunoCAP®-FEIA. Additionally, allergen microarray ImmunoCAP® ISAC analysis was performed. Data were analyzed retrospectively. Results: Twelve out of 19 patients (63% responders) experienced an allergic reaction upon DBPCFC. Overall, 7 patients (37%) developed a significant deterioration of AD with a median increase of 12.4 points in the scoring of atopic dermatitis (SCORAD) index (range 10.0–15.7). Oral allergy syndrome was the predominant immediate-type symptom (n = 11/12 responders). There were no differences in sensitization frequencies regarding allergens of the pathogenesis-related protein family 10 between responders and non-responders. In all patients, correlation of IgE levels determined with ImmunoCAP® ISAC and ImmunoCAP®-FEIA, respectively, was significant with high correlation coefficients regarding birch pollen allergen extract, rBet v 1, and rBet v 2 (r_s > 0.8, p < 0.001) and lower but also significant correlation coefficients regarding food allergens (r_s < 0.8, p < 0.05–<0.001). Conclusion: ImmunoCAP® ISAC microarray allows displaying a differentiated sensitization profile in birch pollen-sensitized patients with AD. However, IgE-mediated sensitization against birch pollen-related allergens revealed by the allergen multiplex system does not predict late eczematous reactions upon DBPCFC with birch pollen-related foods.

Prognostic Significance of Early Leukopenia in Heart Transplant Recipients

<h3>Purpose</h3> Although leukopenia is a relatively frequent finding after heart transplantation, its effects on patient outcomes remain poorly defined. We evaluated the long-term prognostic impact of early leukopenia in this patient population. <h3>Methods</h3> We performed a retrospective single-center cohort study in 133 consecutive heart transplant recipients transplanted between January 2009 and September 2016. Recipients with intensified immunosuppression (IS) and patients who died within the first post-transplant year were excluded. All patients received immunoinduction with basiliximab and maintenence IS therapy with tacrolimus (TAC)/mycophenolate mofetil (MMF)/steroids. Infection prophylaxis consisted of posaconasole (6 months), TMP-SMX (life-long) and valgancyclovir (discontinued pending positive Quantiferon-CMV assay). Early leukopenia was defined as any episode of WBC count <4.0x10⁹/L within 12 months after transplantation. Late CMV reactivation was defined as PCR CMV >1000 IU/mL after discontinuation of virostatic therapy. All patients were followed for 5 years. <h3>Results</h3> Within the first post-transplant year, 47 (35%) patients had at least one episode of leukopenia (Group A) and in 86 (65%) no leukopenia was registered (Group B). The two groups did not differ in gender (male; 77% in Group A vs. 86% in Group B, P=0.12), age (57±10 years vs. 54±11 years, P=0.25), heart failure etiology (ischemic: 41% vs. 42%, P=0.97), the presence of hypertension (68% vs. 61%; P=0.34) and diabetes (32% vs. 24%; P=0.23). IS regimen was comparable in both groups and consisted of TAC (mean C0 level 7.4±1.7 μg/mL vs. 7.2±2.1 μg/mL, P=0.41), MMF (mean dose 1979±100 mg vs. 1994±53 mg, P=0.11) and steroids. However, the duration of valgancyclovir therapy was significantly longer in Group A than in Group B (73±143 days vs. 46±97 days, P=0.001). During follow-up, the patients in Group A were more likely to develop malignancy (21% vs. 6% in Group B, P=0.01). We found no differences in late CMV reactivation (12% in Group A vs. 13% in Group B, P=0.98) and 5-year survival (90% vs. 91%; P=0.88) between the two groups. <h3>Conclusion</h3> In heart transplant recipients early leukopenia episodes are likely related to the prolonged use of virostatic therapy and may be associated with increased rates of post-transplant malignancies.

Too Late Allergic Reaction in a Patient with Permanent Pacemaker.

Contact allergy to cardiac implantable electronic devices is a rare problem in patients. Clinical evaluation and patch tests have an important place in its diagnosis. Also in this case, the diagnosis is supported by ultrasonography. It has been reported in the literature that allergic dermatitis developed after permanent pacemaker implantation in the first few days until the current year. In our case report, we showed that the allergic reaction in the patient was too late. In this article, we present a 94-year-old male patient with a permanent pacemaker who came to us with the complaint of redness and itching in the left chest area and was diagnosed with contact allergy.

Lower levels of CXCL-8 and IL-2 on admission as predictors of early adverse reactions to Bothrops antivenom in the Brazilian Amazon.

Snakebite envenomings are considered a global health problem. The specific therapy for these envenomings consists of administering animal-derived antivenoms aiming to neutralize the venom toxins. Antivenoms have been used effectively to treat snakebites for more than a century; however, their administration may result in early and/or late adverse reactions. The present study presents the prevalence of early adverse reactions (EARs) towards Bothrops antivenom therapy in a health tertiary unit in the Brazilian Amazon and explores if specific plasma cytokines and chemokines from envenomed patients could be used as predictors of EARs. A cohort of patients bitten by Bothrops atrox was followed-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), from 2014 to 2016. Patients were treated with the Brazilian Bothrops antivenom and CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-y, IL-4, and IL-17A were evaluated in patients' plasma samples before and after antivenom administration. From the total of patients (n=186), mostly were male (82.3%), inhabiting rural areas (87.1%), with an average age of 35years. Most of the patients (83.8%) were admitted to the hospital within 6h after the accident, 26 (14%) reported having suffered a previous snakebite, and 97 (52.1%) received between 7 and 9 antivenom vials. The frequency of antivenom-induced EARs was 11.8% (22), resulting mostly of mild reactions. Urticaria was the major EAR manifestation (46.4%). Interestingly, CXCL-8 and IL-2 showed significantly lower levels in patients who progressed to EARs, although IL-2 levels might not represent biological relevance due the small magnitude difference between groups. This study reveals that CXCL-8 and IL-2 could play a role in the onset of EARs in pit viper envenomings.

Result Turnaround Time of RT-PCR for SARS-CoV-2 is the Main Cause of COVID-19 Diagnostic Delay: A Country-Wide Observational Study of Mexico and Colombia.

Delay in COVID-19 diagnosis due to late real-time reverse transcription-polymerase chain reaction reporting has been described to be an important cause of suboptimal COVID-19 surveillance and outbreak containment. The objective of the study was to determine the duration of diagnostic delay due to test turnaround time and its association with marginalization status. In this observational study using national open data of Mexico and Colombia, we quantified the delay in COVID-19 diagnosis that occurred in both countries. We considered two periods that contributed to the delay in diagnosis: the time from symptom onset until testing (delay-one) and test turnaround time (delay-two). Marginalization status was determined according to country-specific scores. Among 3,696,773 patients from Mexico and Colombia, delay-two was generally longer than delay-one. Median delay-one was 3 days and delay-two 7 days in Colombia, while in Mexico, they were 3 days and 4 days, respectively. In Colombia, worse marginalization status prolonged delaytwo. In Mexico, a lower number and percentage of rapid tests were performed in areas with worse marginalization. Diagnostic delay was mostly due to test turnaround time. Marginalization status was an important barrier to diagnostic test access.

Effect of limestone in General Purpose cement on autogenous shrinkage of high strength GGBFS concrete and pastes

This work investigates the autogenous shrinkage of pastes and concretes prepared using General Purpose cement and GGBFS (40% and 60%) up to 100 days. To determine the underlying factors influencing autogenous shrinkage, hydration progression and evolution of microstructure were investigated. Results showed that autogenous shrinkage of GGBFS blends continuously increased after 28 days (until 100 days) whereas the control samples reached a plateau after about 28 days. Late reaction between limestone from the General Purpose cement and alumina from GGBFS progressed untill 90 days forming a high amount of monocarboaluminates. General Purpose cement blends with high GGBFS content can behave as ternary blends and not as binary blends due to the small amount of limestone usually added to General Purpose cements. These long term reactions lead to a significant refinement of the pore structure which is responsible of the late autogenous shrinkage in GGBFS blends.

Late inflammatory reactions in patients with soft tissue fillers after SARS-CoV-2 infection and vaccination: A systematic review of the literature.

IntroductionSoft tissue fillers are used for cosmetic and reconstructive purposes, and soft tissue filler procedures are among the most common nonsurgical procedures in the USA. Although soft tissue filler procedures are relatively quick and safe, adverse events such as late inflammatory reactions have been reported with every filler product. Infections and vaccinations have been proposed as potential triggers for late inflammatory reactions (LIRs), and it is therefore not surprising that these adverse events have been reported after SARS‐CoV‐2 infection and vaccination. Therefore, this review aims to give a detailed overview of these cases.Materials and methodsA literature search was undertaken on LIRs in patients with a history of soft tissue filler use after SARS‐CoV‐2 infection or vaccination. This systematic review was reported according to the PRISMA guidelines. We searched the electronic database PubMed from January 2020 to August 2021. Data on patient characteristics, filler characteristics, clinical findings, and treatment options were included.ResultsThis review included 7 articles with a total of 19 patients with LIRs after SARS‐CoV‐2 infection or vaccination. Three patients with postinfection LIRs and 16 patients with postvaccination LIRs were reported. These LIRS mainly occurred in females who had HA injections for cosmetic purposes. Three patients with postinfection LIRs had symptoms of facial swelling and/or lip angioedema in a matter of weeks. Sixteen patients reported reactions after SARS‐CoV‐2 vaccination (13 following Moderna vaccination and 3 after Pfizer vaccination, after both the first and second doses) from 13 hours up to three weeks. These patients presented with similar clinical symptoms as patients with postinfection LIRs. All patients were treated in a conservative manner.DiscussionThis review shows a relationship between LIRs and SARS‐CoV‐2 infection and vaccination. In the case of vaccination, these adverse events have been reported only after Moderna and Pfizer vaccinations. The reported adverse events are generally minor and self‐limiting, and we encourage patients with soft tissue fillers to participate in vaccination programs.

COVID-19 vaccination including 198 patients with history of severe anaphylactic reaction - own observations.

The SARS-CoV-2 pandemic has taken a heavy toll of 4 million deaths. We were all looking forward to the authorisation of safe vaccines. Soon after vaccination programmes started, the reports about anaphylaxis began to emerge. Growing anxiety has urged regulatory agencies and academic societies to issue adequate recommendations regarding patient eligibility to vaccination. Observation of patients who had a history of a severe anaphylactic reaction and/or anaphylactic shock and were vaccinated against COVID-19. A single-centre, prospective, observational study was conducted at the Department of Infectious Diseases and Paediatrics at Stefan Żeromski Specialist Hospital in Krakow, Poland. Adult patients with a history of a severe anaphylactic reaction and/or anaphylactic shock and patients without it were administered the Comirnaty vaccine by Pfizer-BioNTech or the ChAdOx1-S vaccine by AstraZeneca in a two-dose schedule at the department. The patients were then observed at the department for 60 minutes. A week after each vaccination dose, the patients were contacted by telephone in order to collect data about a late allergic reaction. In total, 403 patients were enrolled. For the Pfizer BioNTech Comirnaty vaccine, the study group (i.e. patients with a history of severe anaphylactic reactions to various substances, other than those present in the vaccine) included 151 patients, and there were 161 controls. For the AstraZeneca ChAdOx1-S vaccine, the study group included 47 patients, and 44 patients formed the control group. Nine cases of severe anaphylactic reactions were reported: 3 in the study groups (1.5%) and 6 in the control groups (3%). Anaphylactic shock after vaccine administration occurred in one patient from the control group. COVID-19 vaccination with using Pfizer-BioNTech Comirnaty and AstraZeneca ChAdOx1-S is safe also for patients with a history of a severe anaphylactic reaction and/or anaphylactic shock. Severe anaphylactic reactions and anaphylactic shock, although rare, may also develop in patients without a prior history of allergic conditions. The Personnel od vaccination centres should be therefore trained to provide medical help. Incorrect patient exclusions delay the attainment of the goal determined for the vaccination programme.

COVID-19 vaccination including 198 patients with history of severe anaphylactic reaction – own observations

INTRODUCTION. The SARS-CoV-2 pandemic has taken a heavy toll of 4 million deaths. We were all looking forward to the authorisation of safe vaccines. Soon after vaccination programmes started, the reports about anaphylaxis began to emerge. Growing anxiety has urged regulatory agencies and academic societies to issue adequate recommendations regarding patient eligibility to vaccination. AIM OF THE STUDY. Observation of patients who had a history of a severe anaphylactic reaction and/or anaphylactic shock and were vaccinated against COVID-19. MATERIAL AND METHODS. A single-centre, prospective, observational study was conducted at the Department of Infectious Diseases and Paediatrics at Stefan Żeromski Specialist Hospital in Krakow, Poland. Adult patients with a history of a severe anaphylactic reaction and/or anaphylactic shock and patients without it were administered the Comirnaty vaccine by Pfizer-BioNTech or the ChAdOx1-S vaccine by AstraZeneca in a two-dose schedule at the department. The patients were then observed at the department for 60 minutes. A week after each vaccination dose, the patients were contacted by telephone in order to collect data about a late allergic reaction. RESULTS. In total, 403 patients were enrolled. For the Pfizer BioNTech Comirnaty vaccine, the study group (i.e. patients with a history of severe anaphylactic reactions to various substances, other than those present in the vaccine) included 151 patients, and there were 161 controls. For the AstraZeneca ChAdOx1-S vaccine, the study group included 47 patients, and 44 patients formed the control group. Nine cases of severe anaphylactic reactions were reported: 3 in the study groups (1.5%) and 6 in the control groups (3%). Anaphylactic shock after vaccine administration occurred in one patient from the control group. CONCLUSIONS. COVID-19 vaccination with using Pfizer-BioNTech Comirnaty and AstraZeneca ChAdOx1-S is safe also for patients with a history of a severe anaphylactic reaction and/or anaphylactic shock. Severe anaphylactic reactions and anaphylactic shock, although rare, may also develop in patients without a prior history of allergic conditions. The Personnel od vaccination centres should be therefore trained to provide medical help. Incorrect patient exclusions delay the attainment of the goal determined for the vaccination programme.

A novel coal gangue thermal stabilizer and its effect on thermal stability and mechanical properties of poly(vinyl chloride)

AbstractNontoxic and efficient coal gangue thermal stabilizer (Y‐CG) was prepared by cheap and readily available calcium oxide, coal gangue (CG) and stearic acid(SA). The proposed mechanism of Y‐CG thermal stability was studied by XRD, FT‐IR, BET and thermal stability test. The results show that when the mass ratio of CG to water was 1:7, the loading of Ca(OH)2 between CG sheets reached the maximum value of 3.01 mmol/g. The hydrophobic property of the Y‐CG surface was better when modified at 75°C for 2 h with 5% SA. With 10% Y‐CG, the Congo red test showed thermal stabilization time of PVC improved up to 55.9 min and the torque rheological test showed dynamic thermal stabilization time of PVC improved up to 62.10 min. The TG curves show that Y‐CG had little effect on the onset degradation temperature of PVC. Still, Y‐CG can absorb HCl and initiate the carbonization of PVC to inhibit degradation. Compared with the commonly used thermal stabilizers, the thermal stability of Y‐CG was only slightly worse than that of hydrotalcite thermal stabilizers. The early reaction was that the strong base Ca(OH)2 in Y‐CG adsorbs HCl, and the CaCl2 was stably loaded in the CG layered structure, which avoided the adverse effects caused by strongly alkaline. The late reaction was that SA and Ca(OH)2 form weakly alkaline calcium stearate to absorb HCl. At the same time, calcium stearate can also be used as a compatibilizer to improve the compatibility between Y‐CG and PVC.

MAS-1, a novel water-in-oil adjuvant/delivery system, with reduced seasonal influenza vaccine hemagglutinin dose may enhance potency, durability and cross-reactivity of antibody responses in the elderly

BackgroundIncreased influenza vaccine efficacy is needed in the elderly at high-risk for morbidity and mortality due to influenza infection. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. MethodsA phase 1, randomized, double-blind, safety and immunogenicity, adjuvant dose escalation trial was conducted in persons aged 65 years and older. MAS-1 adjuvant dose volumes at 0.3 mL or 0.5 mL containing 9 µg per HA derived from licensed seasonal trivalent influenza vaccine (IIV, Fluzone HD 60 µg per HA, Sanofi Pasteur) were compared to high dose (HD) IIV (Fluzone HD). Safety was measured by reactogenicity, adverse events, and safety laboratory measures. Immunogenicity was assessed by serum hemagglutination inhibition (HAI) antibody titers. ResultsForty-five subjects, aged 65–83 years, were randomly assigned to receive 9 µg per HA in 0.3 mL MAS-1 (15 subjects) or HD IIV (15 subjects) followed by groups randomly assigned to receive 9 µg per HA in 0.5 mL MAS-1 (10 subjects) or HD IIV (5 subjects). Injection site tenderness, induration, and pain, and headache, myalgia, malaise and fatigue were common, resolving before day 14 post-vaccination. Clinically significant late-onset injection site reactions occurred in four of ten subjects at the 0.5 mL adjuvant dose. Safety laboratory measures were within acceptable limits. MAS-1-adjuvanted IIV enhanced mean antibody titers, mean-fold increases in antibody titer, and seroconversion rates against vaccine strains for at least 168 days post-vaccination and enhanced cross-reactive antibodies against some non-study vaccine influenza viruses. ConclusionMAS-1 adjuvant provided HA dose-sparing without safety concerns at the 0.3 mL dose, but the 0.5 mL dose caused late injection site reactions. MAS-1-adjuvanted IIV induced higher HAI antibody responses with prolonged durability including against historical strains, thereby providing greater potential vaccine efficacy in the elderly throughout an influenza season.Clinical Trial Registry: ClinicalTrials.gov # NCT02500680.

Late Skin Reactions Associated with the Modern Vaccine

The infection by the SARS-CoV-2 virus and the disease generated by COVID-19 that began in 2019 in Wuhan China has had a great impact on global morbidity and mortality, which in turn led to the creation in record time of the first vaccines used in humans against coronavirus. Vaccines such as Sinovac, Janssen, AstraZeneca, Pfizer and Moderna, of which have been authorized and administered in multiple countries with really favorable results. However, late post-vaccination adverse effects have been reported in patients vaccinated especially by Moderna and Pfizer, observing a compromise at the level of the skin causing the appearance in most cases of urticaria, edema, erythema, reactivation of herpes zoster, morbilliform eruptions, among others that are undoubtedly related to the mechanisms of action of the aforementioned vaccines.

Effect of neurofeedback training on auditory evoked potentials’ late components reaction time: A placebocontrol study

Background/Aim. Sensorimotor rhythm (SMR) neurofeedback training contributes to improving cognitive performance, increasing attention. SMR power is increased when a person is focused and task-oriented. The shorter reaction time of the P300 evoked potentials (AEPs) are associated with better attention. Hence, the increase in SMR power after NFB SMR training should decrease the reaction time in a cognitive task. This study aimed to examine the ability of healthy individuals to modulate the sensorimotor (SM) rhythm of electroencephalographic activity between 12 and 15 Hz during 20-day neurofeedback (NFB) training sessions. In addition, the effect of NFB sensorimotor rhythm training on reaction time (RT) was investigated. Methods. Participants were divided into control and experimental groups, with 24 subjects (12 males) aged between 25 and 40 years. Participants in the experimental group were trained with authentic SM rhythm NFB training, while in the control group false (placebo) training was applied. Auditory evoked potentials (AEPs) were registered on 5 occasions: before NFB training, after 5, 10, and 20 training sessions, and one month after the last training. Results. The results showed that a series of 20 SM rhythm NFB training increases the amplitudes of the SM rhythm. RT in the experimental group was significantly shortened, while in the control group it was not observed. Also, the increase in the power of the EEG signal of the SM rhythm showed a negative correlation with RT, but only in a subgroup of male subjects. Conclusion. The obtained results indicate the effects of NFB training on the improvement of the attention process expressed by reaction time.