Late Reactions Research Articles

Preparation and characterization of low-activity coal bottom ash-based cementitious materials via orthogonal experiment

The effective use of coal bottom ash produced by burning coal can reduce the pollution of solid waste to land and water resources. Meanwhile, the use of coal bottom ash as cementitious materials can reduce the demand for traditional resources and carbon emissions, availing to promoting the sustainable development of the construction industry. However, the application and popularization of coal bottom ash-based cementitious materials are facing many practical problems. For example, the utilization rate of coal bottom ash is low, and the traditional alkali activation method has some limitations such as high cost and poor safety. For this reason, through orthogonal experiment and range analysis, new calcium combination activators were explored for the preparation and optimization of coal bottom ash-based cementitious materials. The coal bottom ash-based cementitious materials with compressive strength up to 17 MPa was prepared, when the mass ratio of CaO: Ca(OH)2: AlPO4 was 1: 0.15: 0.10 : 0.05 and preparation temperature was 15 °C. Furthermore, the influence of various factors on the compressive strength of the products was evaluated comprehensively: AlPO4 > CaO and Ca(OH)2 > preparation temperature. The action effect and reaction mechanism of various factors were revealed by means of fluidity test, setting time test, XRD, FTIR and SEM-EDS. The results show that calcium combination activators react with coal bottom ash to mainly form C-A-S-H gel. Among the calcium combination activators, CaO greatly improves the rate of early hydration reaction, Ca(OH)2 is conducive to the sustained and stable development of late hydration reaction, and AlPO4 can improve the fluidity and setting time of the slurry. Moreover, although the water and environment temperature show the weakest influence in the laboratory stage, the influence of this factor on the property of the cementitious materials in the actual project cannot be ignored. This research has important scientific and engineering significance for promoting coal bottom ash-based cementitious materials in economic development and environmental protection.

A single-center experience of the upright proton therapy for skull-base chordomas and chondrosarcomas: Updated results

AimTo access efficacy and safety of the upright proton therapy for the skull-base chordomas and chondrosarcomas. Materials and methodsThe study encompasses single-center experience of proton therapy in chordomas (CA) and chondrosarcomas (CSA) of skull-base localization. We evaluate overall survival, local control and toxicity. Tumor response was assessed in accordance with RANO criteria. Treatment-related toxicity was evaluated with the help of CTCAE v 5.0 scale. ResultsProton therapy in the upright position was utilized for 51pts (patients) with CA-CSA (40 pts with chordoma and 11pts with chondrosarcoma) at the A. Tsyb Medical Radiological Research Center in 2016–2023. Median tumor volume constituted 30 cm3 (IQR (interquartile range) 15–41 cm3). Median total dose was 70 GyRBE. Median number of fractions was 35. Overall survival (OS) at 1-, 2- and 3-year rates reached 98.0 %, 88.6 % and 82.7 %, respectively. Median follow-up time was 36 months. The 1-, 2- and 3-year local control (LC) rates constituted, respectively, 98 %, 78.6 % and 66.3 %. Prior surgery showed statistically significant association with better prognosis (p = 0.023). Brainstem-to-tumor dose coverage compromise became the major pattern of LC failure (p = 0.03). The late radiation toxicity reactions included temporal lobe necrosis grade 2 in 2 pts, xerostomia grade 1 in 1pt, radiation cataract grade 2 in 1pt and persistent headache grade 2 in 4 pts. Severe late toxicity reactions were observed in 2 cases (4 %): 1 myelitis grade 3 and brainstem damage grade 5 in 1pt. ConclusionLocal control was achieved in the majority of patients receiving the scanning-beam upright proton therapy for skull-base CA-CSA. The LC rates after a surgery-radiotherapy combination treatment were higher compared with irradiation alone. Pattern of failure is mostly brainstem-tumor dose compromise. The high OS and LC rates were accompanied by low toxicity incidence. Even in complex case of the skull base CA-CSA upright proton therapy shows promising clinical outcomes.

Metal-Catalyzed Thermo-Catalytic Decomposition and Continuous Catalyst Generation

In this study, metal dusting is utilized to initiate a two-stage thermo-catalytic decomposition (TCD) process. Stage 1 starts with metal-catalyzed TCD, and in stage 2 the metal-catalyzed carbon catalyzes additional TCD. TEM is presented of the early- versus late-stage TCD to qualitatively illustrate the second-stage TCD by the metal-catalyzed carbons. Corresponding SEM illustrates differences in growth type and surface density between early versus late reaction times, with backscattered imaging differentiating the first- versus second-stage TCD. TGA supports the microscopic inference of a second carbon phase by the presence of an early (low-temperature) reaction peak, characteristic of low-structure or disordered carbon as the second-stage TCD carbon. Raman analysis confirms that the second-stage carbon deposit is more disordered and unstructured, especially at 1000 °C, supported by the ID/IG and La value changes from 0.068 to 0.936 and 65 nm to 4.7 nm, respectively. To further confirm second-stage TCD occurrence upon pre-catalyzed carbons, two carbon blacks are tested. Exposing a combination of edge and basal or exclusively basal sites for the graphitized form, they afford a direct comparison of TCD carbon nanostructure dependence upon the initial carbon catalyst nanostructure. Pre-oxidation of the stainless-steel wool (SSW) prior to TCD is advantageous, accelerating TCD rates and increasing carbon yield relative to the nascent SSW for an equivalent reaction duration.

RADT-02. PROTON THERAPY IN PEDIATRIC ONCOLOGY IN SLOVAKIA: A COMPREHENSIVE ANALYSIS

Abstract INTRODUCTION Radiotherapy has been a cornerstone in pediatric oncology for decades. Recognizing the potential to mitigate side effects, proton therapy (PT) has gained prominence, becoming part of treatment in pediatric oncology in Slovakia since 2014. METHODOLOGY This retrospective analysis investigates a cohort of patients with CNS tumors treated at the National Institute of Children’s Diseases in Bratislava, who underwent PT at the Proton Center in Prague between 2014 and 2022. RESULTS Among 47 patients, embryonal tumors constituted the largest group (40%), followed by germ cell tumors (21%), ependymal tumors (19%), less common CNS tumors (10%), and glial tumors (8%). Acute complications included skin toxicity (38%), CNS toxicity (23%), GIT toxicity (14%), and blood count changes (8%). Notably, 22 patients experienced no acute toxicity. Late reactions, predominantly endocrine dysfunction (65%), featured central hypothyroidism (45%), ACTH deficiency (22%), GH deficiency (16%), and gonadotropin deficiency (10%). Ocular complications affected 55%, while tensive cephalea and post-radiation necrosis-related epileptic seizures were observed in limited cases. Disease recurrence was absent in 89% of patients, with 10% exiting due to disease progression. CONCLUSION This pioneering analysis highlights the unique experiences of Slovak pediatric patients undergoing PT at the Proton Center in Prague. The study emphasizes the dual impact of PT, enhancing survival rates while reducing adverse effects, thereby significantly contributing to a better quality of life for pediatric cancer patients.

Assertive China After the Rise of Xi Jinping

In terms of China's internationalisation and economic policy, the Chinese economic miracle, which supports visions of China as a global hegemon, would correspond to a coherent long-term grand strategy. First, we analyse the key drivers along China's partial liberalisation processes. Second, the focus will shift to recent political developments in the West, as a late reaction to a more assertive China and its 'wolf diplomacy', taking into account the weakness of the free world in the face of the China threat, given the apparent strengths identified in the examination of China's strategy. Finally, a brief section will be devoted to general conclusions integrating the results of the two perspectives.

Abstract PO1-22-03: Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy

Abstract Introduction: Previous studies have shown that ATM (ataxia-telangiectasia mutated) mutations may be associated with increased radiation sensitivity and altered treatment response. However, there is a limited understanding of the clinical implications and optimal management strategies for breast cancer patients with ATM mutations receiving radiotherapy (RT). The aim of our study is to assess the impact of ATM mutations on radiation response and treatment outcomes in breast cancer patients undergoing RT. Material and Methods: A total of 79 female patients diagnosed with breast cancer were included in the study, with 31 (39.3%) having pathogenic (P) and likely pathogenic (LP) variants (all of the variants were heterozygous) and 48 (60.8%) having VUS variants detected through whole ATM gene sequencing screening for patients in accordance with NCCN clinical practice guideline. Statistical analysis, including descriptive, graphical, and inferential methods, such as the Kolmogorov-Smirnov test, Mann-Whitney U Test, and Chi-square tests, was conducted using SPSS version 25.0 to evaluate the normal distribution of continuous variable scores and perform quantitative and qualitative comparisons between groups at a 95% confidence level (p < 0.05). Results: The median age of the patients was 44 years (range: 24-74), with 75% of them being 50 years old or younger .The rate of breast cancer in patients with VUS variants was significantly higher in those aged 50 and below compared to those with P/LP variants (83% vs. 61%, p=0.028). There was no statistically significant difference in clinical stage, tumour histological type, and molecular subtype classification based on ATM gene variant type (P/LP vs. VUS) among the patients (p>0.05), but the rate of high tumour grade was significantly higher in the VUS variant group (65% vs. 40%, p=0.034). The rate of patients who received RT was 87%, with 26 patients receiving radiation to the breast or chest wall and 43 patients receiving additional regional lymph node irradiation. There were no statistically significant differences in surgical and systemic treatment types and RT dose based on ATM gene variant type (P/LP vs. VUS) (p>0.05). Among the patients who received RT, 33 (48%) experienced early-stage skin reactions, and 15 (22%) experienced late-stage skin reactions according to Common Terminology Criteria for Adverse Events (CTCAE) v5. No Grade 3, 4 and 5 early and late toxicity were observed . The rate of early (83% vs. 23%; p< 0.001) and late (35% vs. 13%; p=0.029) skin reactions was significantly higher in the P/LP variant group compared to the VUS variant group. Grade I lymphedema was observed in 2 (2.5%) patients, 1 (3.2%) in the P/LP group and 1 (2.1%) in the VUS group (p>0.05). Among the 23 patients who underwent breast reconstruction, 1 (4%) had implant revision and 1 (4%) experienced implant loss, both of which were observed in the pathogenic variant group (p>0.05). Conclusion: Limited clinical data exists on RT toxicity in breast cancer patients with ATM gene mutations, and clear guidelines for decision-making are lacking. Our study revealed higher rates of acute and chronic skin reactions in the P/LP variant group, highlighting the need for further investigation into the impact of these variants on treatment outcomes and patient management. However, it is crucial to manage these reactions effectively and not allow them to hinder treatment. Additional research and interventions are warranted to better understand and address these reactions, aiming to enhance the overall treatment experience and outcomes for patients with ATM gene mutations. Citation Format: Evrim Tezcanli, Seda Eroz, Ugur Ozbek, Ahmet Yesilyurt, CIHAN URAS, Nuran Bese. Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-03.

Adverse reactions after intravascular iodinated contrast media administration and their management.

Endovascular interventions and diagnostic examinations using iodinated contrast media (ICM) are standard of care in current vascular medicine. Although ICM use is generally considered safe, it may be associated with adverse reactions, vary from minor disturbances to rare, but severe life-threatening complications. This position paper of European Society of Vascular Medicine integrates current knowledge and summarizes the key information related to the use of intravascular ICM, serving as recommendation on prevention and management of acute, late, and very late adverse reactions. It should help the health professionals in all fields of vascular medicine to make decisions in daily practice for safe use of contrast media.

The latest Jurassic–earliest Cretaceous climate and oceanographic changes in the Western Tethys: The Transdanubian Range (Hungary) perspective

AbstractThe Jurassic/Cretaceous transition was characterized by several distinct palaeoenvironmental processes and events, amongst which some of the best known are the late Tithonian–early Berriasian aridization and the late Berriasian tectonic reactivation in the Neotethyan Collision Belt. This study aims to reconstruct the latest Jurassic–earliest Cretaceous palaeoenvironment and its evolution in the area of the Transdanubian Range (Hárskút and Lókút successions, Hungary), and provide new data on the relation between climate changes, palaeoceanography and marine ecosystems. Herein, calcareous nannofossil and geochemical data are presented and put into a geochronological framework in order to evaluate and compare palaeoenvironmental signals recorded in the two studied successions; the resultant scenario is compared with published literature data from both the western Tethyan region and northern Europe. Accordingly, in the Transdanubian Range, the relatively humid climate of the early Tithonian was followed by the late Tithonian–early Berriasian arid phase and the late Berriasian humidification. Besides, two intervals of palaeoceanographic perturbations were documented in the upper Tithonian–lowermost Berriasian (OD I), and the lower/upper Berriasian transition beds (OD II); these are manifested by the record of seafloor hypoxia and elevated accumulations of micronutrients, as well as changes in calcareous nannofossil assemblages. In the view of this study, the most probable trigger of the late Tithonian–early Berriasian aridization was a restriction in the atmospheric circulation (including monsoons), which was forced by climate cooling and lowering thermal gradient between landmasses and the ocean. Under such conditions, the mechanism of a wind‐induced water mixing might become less efficient, driving seawater stratification, seafloor hypoxia and increased burial of nutrients. Although the humid climate of the late Berriasian likely resumed the monsoon‐type circulation, the tectonic reactivation and uplift in the NeoTethyan Collision Belt might have effectively separated the Bakony Basin from the ‘open’ NeoTethys, which hampered the marine circulation and efficient water mixing in the former.

Immune response profiles from humans experimentally exposed to Phlebotomus duboscqi bites.

Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease. To characterize the human immunological responses developed against saliva of Phlebotomus duboscqi, a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining. A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens. Our results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine.

Late Tuberculosis Reactivation After Severe Covid-19.

Although there is no specific therapy for COVID-19, it is recommended that patients with severe SARS-CoV-2 infection are treated with corticosteroids and anti-IL-6 receptor monoclonal antibodies. Both COVID-19 itself and the treatment modalities mentioned above have suppressive effects on the immune system which may lead to an increased susceptibility to other infections. In patients with latent tuberculosis (TB) reactivation of TB infection after recovery from severe COVID-19 has been described. Most of these cases have occurred in parts of the world where tuberculosis is endemic. The patient is a female in her 70s who was born and raised in Southeast Asia and has lived in the Netherlands for more than 30 years. She was treated for a severe COVID-19 requiring mechanical ventilation for several weeks and pharmaceutical treatment with corticosteroids and anti-IL-6 receptor monoclonal antibodies (Sarilumab). She recovered well. Two years later she was readmitted with symptoms of a serious pulmonary infection and meningitis. Her condition deteriorated in a short time. An active TB infection was diagnosed. Despite adequate antibiotic treatment and supportive therapy her condition worsened and four days after admission to the ICU she deceased. Reactivation of latent TB after recovery from a severe COVID-19 has been described several times and may occur several months after the SARS-CoV-2 infection. In this case the reactivation presented two years after COVID-19. This case illustrates that long-term follow-up of patients with latent TB that recover from a severe COVID-19 may be indicated. Reactivation of latent tuberculosis infection in patients treated for a severe COVID-19 may occur even two years after recovery from SARS-CoV-2 infection.Most cases of reactivation of tuberculosis after COVID-19 are described in regions where tuberculosis is endemic. However, it may also occur in countries with a relatively low prevalence of tuberculosis infection. The exact incidence of tuberculosis reactivation after COVID-19 is unknown and probably underestimated.A long-term follow-up of patients after severe COVID-19 treated with corticosteroids and/or anti-IL-6 receptor monoclonal antibodies with a history of tuberculosis or patients migrated from countries where tuberculosis is endemic seems to be important.

Detection of iodixanol-induced allergic reaction signals in Chinese inpatients: a multi-center retrospective database study using prescription sequence symmetry analysis.

This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection. A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method. 126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories-calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines-as marker drugs. With time intervals of 3, 7, and 28days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08-2.15), 1.70 (95% CI: 1.68-1.73), 3.85 (95% confidence interval [CI]: 3.75-2.30), 2.30 (95% CI: 2.26-2.35), and 1.95 (95% CI: 1.89-2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%-3%), calcium gluconate (0.19%-0.52%), adrenergic/dopaminergic agents (2.20%-3.37%), glucocorticoids (3.13%-3.76%), and antihistamines (1.05%-1.32%). This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with ≤7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs.

Incidence and factors associated with early and late adverse reactions after the first dose of Pfizer-BioNTech vaccine among healthcare workers

Incidence and factors associated with early and late adverse reactions after the first dose of Pfizer-BioNTech vaccine among healthcare workers

Characterization of the Pro-Inflammatory and Pruritogenic Transcriptome in Skin Lesions of the Experimental Canine Atopic Acute IgE-Mediated Late Phase Reactions Model and Correlation to Acute Skin Lesions of Human Atopic Dermatitis.

Intradermal injection of anti-immunoglobulin E (IgE) antibodies in dogs grossly and histologically resemble naturally occurring atopic dermatitis (AD). However, the activated inflammatory and pruritic pathways have not been characterized. The objectives of this study were to characterize the inflammatory transcriptome of experimental acute canine IgE-induced lesions and to determine how these correlate to the transcriptome of naturally occurring human and canine acute atopic dermatitis. Biopsies were collected at 6 and 24 h after intradermal injections of anticanine-IgE antibodies to eight healthy male castrated Beagles; healthy and saline-injected skin served as controls. We extracted total RNA from skin biopsies and analyzed transcriptome using RNA-sequencing. Gene expressions of IgE-induced biopsies were compared to that of controls from the same subject (1.5-fold change, p-adjusted value ≤ 0.05). Acute IgE-mediated lesions had a significant upregulation of pro-inflammatory (e.g., LTB, IL-1B, PTX3, CCL2, IL6, IL8, IL18), T helper-(Th)1/IFNγ signal (e.g., STAT-1, OASL, MX-1, CXCL10, IL-12A) and Th2 (e.g., IL4R, IL5, IL13, IL33 and POSTN) genes, as well as Th2 chemokines (CCL17, CCL24). Pathway analysis revealed strong significant upregulation of JAK-STAT, histamine, IL-4 and IL13 signaling. Spearman correlation coefficient for the shared DEGs between canine anti-canine-IgE and human AD samples revealed a significant moderate positive correlation for anti-canine-IgE 6-h samples (r = 0.53) and 24-h samples (r = 0.47). In conclusion, acute canine IgE-mediated skin lesions exhibit a multipolar immunological axis upregulation (Th1, Th2 and Th17) in healthy dogs, resembling acute spontaneous human AD lesions.

Comparing reactivation and retreatment for three doses of bevacizumab in type 1 retinopathy of prematurity

To determine timing and rates of reactivation and retreatment of type 1 retinopathy of prematurity (ROP) after treatment with either 0.125 mg, 0.250 mg, or 0.500 mg of intravitreal bevacizumab (IVB). Retrospective data, including demographic information, past medical history, and ROP characteristics were analyzed for babies with type 1 ROP treated with IVB at Riley Hospital for Children for the perioed 2014-2021. A total of 84 patients met inclusion criteria: 29 patients received 0.125 mg of IVB; 39, 0.250 mg; and 16, 0.500 mg. Of the 84, 67 (80%) had additional laser treatment because of late reactivation (n = 52) or persistent avascular retina (PAR) (n = 15). Subsequent laser treatment was more common with lower doses: 0.125 mg (n = 27 [93%]); 0.250 mg (n = 31 [80%]); 0.500 mg (n = 9 [57%]) (P = 0.012). There was no difference between groups with regard to reason for subsequent laser treatment (reactivation vs PAR). The 0.125 mg group required retreatment because of reactivation 3.8 weeks sooner than the other dosing groups (P = 0.047). The outcomes comparing three doses of IVB for severe ROP showed a difference in the timing of secondary treatment, with the lower dosing group requiring laser for reactivation earlier.

A case of retained surgical mop in abdomen with partial intragastric migration: a case report

Though not uncommon, to retain a foreign body in the abdomen is a preventable error that makes the life of a patient miserable. One of the commonest retained foreign bodies is surgical mop or sponge. Retained mop may cause either an early septic reaction or a late fibrotic reaction. They often cause sinus or fistula and even can transmigrate in to the lumen of viscera. In case of upper abdominal retained mops, they usually erode the thin duodenal wall and rarely stomach. In this case, a mop was retained in the deep subhepatic space 2.5 months ago following open cholecystectomy. It caused an aseptic fibrotic reaction resulting in encapsulation of the mop. It then eroded the antral part of stomach through the lesser curvature and caused luminal obstruction. The patient presented with vomiting after each meal. Upper gastrointestinal tract (GIT) endoscopy revealed a woven fabric object that was impacted and occluded the lumen. The retained mop was removed after laparotomy and the antral wall was repaired well. This case is noteworthy due to its less symptom and penetration into the stomach.

Skin dose-volume predictors of moderate-severe late side effects after whole breast radiotherapy

BackgroundToxicity after whole breast Radiotherapy is a relevant issue, impacting the quality-of-life of a not negligible number of patients. We aimed to develop a Normal Tissue Complication Probability (NTCP) model predicting late toxicities by combining dosimetric parameters of the breast dermis and clinical factors. MethodsThe skin structure was defined as the outer CT body contour's 5 mm inner isotropic expansion. It was retrospectively segmented on a large mono-institutional cohort of early-stage breast cancer patients enrolled between 2009 and 2017 (n = 1066). Patients were treated with tangential-field RT, delivering 40 Gy in 15 fractions to the whole breast. Toxicity was reported during Follow-Up (FU) using SOMA/LENT scoring. The study endpoint was moderate-severe late side effects consisting of Fibrosis-Atrophy-Telangiectasia-Pain (FATP G ≥ 2) developed within 42 months after RT completion. A machine learning pipeline was designed with a logistic model combining clinical factors and absolute skin DVH (cc) parameters as output. ResultsThe FATP G2 + rate was 3.8 %, with 40/1066 patients experiencing side effects. After the preprocessing of variables, a cross-validation was applied to define the best-performing model. We selected a 4-variable model with Post-Surgery Cosmetic alterations (Odds Ratio, OR = 7.3), Aromatase Inhibitors (as a protective factor with OR = 0.45), V20 Gy (50 % of the prescribed dose, OR = 1.02), and V42 Gy (105 %, OR = 1.09). Factors were also converted into an adjusted V20Gy. ConclusionsThe association between late reactions and skin DVH when delivering 40 Gy/15 fr was quantified, suggesting an independent role of V20 and V42. Few clinical factors heavily modulate the risk.

Safety and Tolerability of COVID-19 Vaccine in Mast Cell Disorders Real-Life Data from a Single Centre in Italy.

Background In the past three years, COVID-19 has had a significant impact on the healthcare systems and people's safety worldwide. Mass vaccinations dramatically improved the health and economic damage caused by SARS-CoV-2. However, the safety of COVID-19 vaccines in patients at high risk of allergic reactions still has many unmet needs that should be clarified. Material and methods A retrospective, single-centre study was performed by collecting demographic and clinical data of patients with Mast Cell Disorders (MCDs) to evaluate the safety and tolerability of COVID-19 vaccinations. Moreover, any changes in the natural history of the underlying disease following the vaccine have been evaluated. Results This study included 66 patients affected with MCDs. Out of them, 52 (78.8%) received a COVID-19 vaccination and 41 (78.8%) completed the vaccination course. Premedication came first in 86.6% of our patients. A total of seven (4.5%) patients complained about an immediate reaction and two (1.3%) had a late reaction. Worsening of MCD history was observed in a single patient. Conclusions Despite the overall high risk of allergic reactions, our study did not reveal any increased risk for SARS-CoV-2 allergic reactions in MCD patients, thus supporting the recommendation in favour of the SARS-CoV-2 vaccination. However, due to the potentially increased rate of anaphylactic reactions, MCD patients should receive vaccine premedication and should be treated in a hospital setting after an allergological specialistic evaluation.

Impaired T cells and “memory-like” NK-cell reconstitution is linked to late-onset HCMV reactivation after letermovir cessation

AbstractAllogeneic hematopoietic stem cell transplantation (alloSCT) is the only cure for many hematologic malignancies. However, alloSCT recipients are susceptible to opportunistic pathogens, such as human cytomegalovirus (HCMV). Letermovir prophylaxis has revolutionized HCMV management, but the challenge of late HCMV reactivations has emerged. Immunological surrogates of clinically significant HCMV infection (csCMVi) after discontinuation of letermovir remain to be defined. Therefore, we studied natural killer (NK)-cell reconstitution along with the global and HCMV pp65-specific T-cell repertoire of 24 alloSCT recipients at 7 time points before (day +90) and after (days +120-270) cessation of letermovir prophylaxis. Patients who experienced csCMVi had lower counts of IFN-γ+ HCMV–specific CD4+ and CD8+ T cells than HCMV controllers. Furthermore, patients with csCMVi displayed late impairment of NK-cell reconstitution, especially suppression of “memory-like” CD159c+CD56dim NK-cell counts that preceded csCMVi events in most patients. Moreover, several surrogates of immune reconstitution were associated with the severity of HCMV manifestation, with patients suffering from HCMV end-organ disease and/or refractory HCMV infection harboring least HCMV–specific T cells and “memory-like” NK cells. Altogether, our findings establish an association of delayed or insufficient proliferation of both HCMV–specific T cells and “memory-like” NK cells with csCMVi and the severity of HCMV manifestations after discontinuation of letermovir prophylaxis.

Postoperative Intensity Modulated Radiotherapy for Acinic Cell Parotid Carcinoma in Childhood- A Clinical Case from our Practice with Literature Review

Malignant parotid tumors in childhood are extremely rarely diagnosed diseases. Due to the rare incidence, there is no consensus on their complex treatment, as well as on the application of postoperative radiation therapy (RT). We present a clinical case of acinic cell parotid carcinoma in a 12-year-old girl, against the background of which we emphasize the optimal complex therapeutic approach. Despite radical facial nerve-sparing parotidectomy in pT2N0 acinic cell parotid carcinoma, due to the two pathohistological negative factors/two foci with vascular tumor invasion and the close proximity of the resection line to the preserved facial nerve, we conducted postoperative adjuvant RT. Due to the risk of late radiation reactions of normal tissues and organs after RT in childhood, intensity modulated radiation therapy (IMRT) with lower radiation doses in the target volumes was performed. Active surveillance and follow-up imaging studies are required for early diagnosis of possible recurrence or distant metastases.

MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction.

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma's pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1, VEGFA, and GSK3B, which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR.