Predictive Factors of Immunotherapy in Gastric Cancer: A 2024 Update.

Many studies on gastric cancer treatment have identified predictors of immunotherapy benefits. This article provides an update on the major developments in research related to predictive factors of immunotherapy for gastric cancer. We used the search term "predictive factors, immunotherapy, gastric cancer" to find the most current publications in the PubMed database related to predictive factors of immunotherapy in gastric cancer. Programmed cell death, genetic, and immunological factors are the main study topics of immunotherapy's predictive factors in gastric cancer. Other preventive factors for immunotherapy in gastric cancer were also found, including clinical factors, tumor microenvironment factors, imaging factors, and extracellular factors. Since there is currently no effective treatment for gastric cancer, we strongly propose that these studies be prioritized.

Managing Severe Adverse Reactions to Biologicals in Severe Asthma.

BACKGROUND: The use of biological agents in the treatment of various inflammatory and malignancy conditions has expanded rapidly. However, these agents can induce hypersensitivity reactions, posing significant clinical challenges. METHODS: We conducted a retrospective study that included nine patients with severe asthma who experienced hypersensitivity reactions to biological agents (omalizumab, benralizumab and dupilumab). RESULTS: Hypersensitivity reactions to biologicals in severe asthma were observed in 9 of 68 patients treated. In five cases, treatment was stopped or changed to another available biological, and for four patients administered under close surveillance, titrated provocation or desensitization was applied. Successful desensitization was achieved in three of the patients, allowing them to continue therapy without adverse reactions. Improvements in asthma control were observed post-desensitization, leading to the reduced need for systemic steroid treatments and an increase in quality of life. CONCLUSIONS: This study highlights the importance of recognizing hypersensitivity reactions to biologicals to have an appropriate approach for patients with severe asthma. As an effective approach for patients experiencing hypersensitivity reactions to biological agents, desensitization allows treatment continuation.

IL-31-Pruritus Interleukin: Serum Values and Clinical Impact in Chronic Spontaneous Urticaria-A Romanian Retrospective Study.

(1) Background: This study aimed to evaluate the implications of interleukin-31 (IL-31) in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters that were identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the accepted international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Significantly elevated serum IL-31 levels were observed in CSU patients compared to the controls (p < 0.0001). Although no direct correlations were found between IL-31 and inflammatory markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)), eosinophils, or total immunoglobulins E (IgE), significant differences in IL-31 levels were identified based on CSU severity, quality of life impact, itch intensity, and response to histamine H1 receptor antagonists (H1 antihistamines) (p < 0.05 for all). (4) Conclusions: Our findings underscore that IL-31 is not directly associated with general inflammation, eosinophilic response, or atopy in CSU. Nevertheless, its expression is influenced by key disease characteristics: severity, pruritus, and H1 antihistamine response. This investigation provides essential insights into CSU pathogenesis, potentially leading to novel therapeutic interventions. An enhanced understanding of these mechanisms is crucial due to the limitations of current treatment modalities in terms of fully managing CSU symptoms.

A retrospective study regarding the influence of COVID-19 disease on asthma.

BACKGROUND: During the Covid-19 pandemic patients suffering from asthma raised many concerns regarding the outcome ofthe impact of COVID-19 disease on their preexisting condition. The 2021 GINA report indicates that people with asthma do not appear to be at increased risk of a severe form of COVID-19. METHOD: This study is a retrospective study of patients (n = 163) median age = 27.8 years, M:F = 1:1.26, with asthma evaluated using ACT (asthma control test) and VAS (visual analog scale) before and after COVID-19 disease. An ACT score over 20 points placed patients in the controlled asthma group. RESULTS: The overall evaluation for COVID-19 in our asthma patients revealed that 22.7% of the studied group had the COVID-19 disease (21.5% in the controlled asthma group and 24.5% in uncontrolled asthma group). Asthma disease history was longer in the uncontroled asthma group (128 ± 96.8 months vs. 296 ± 59.7 months, p = 0.05). Asthma treatment was conducted according to the GINA guideline, and 18.4% (30 pts) of the patients were on allergen immunotherapy treatment. Significantly more uncontrolled patients were significantly more in Step 1 and 5 of treatment (p = 0.05 and p = 0.03). During the COVID-19 pandemic, patients in the GINA step 5 of treatment experienced a worsening of asthma, often twice as severe as compared to patients with asthma in GINA step 1-4. In these patients, even mild COVID-19 disease led to worsened asthma symptoms, while severe COVID-19 led to a severe asthma impairment measured by ACT score (p = 0.03) and VAS scale (p = 0.02), with increased oral corticosteroids consumption. CONCLUSION: Maintaining optimal asthma control should be able to reduce risk of severe outcomes after COVID-19 disease. Communication via phone with the specialist involved in their asthma care was very comforting for patients, thus confirming the necessity to include phone calls, smart phone's application or online evaluations and counseling in long-term care of chronic diseases.

Off-Label Benralizumab in Severe Non-Necrotizing Eosinophilic Vasculitis following Critical COVID-19 Disease and in DRESS.

Benralizumab is a humanized recombinant mAb that binds to the interleukin 5 receptor (IL-5R) expressed on eosinophils and is approved for the treatment of severe eosinophilic asthma. There are a series of severe eosinophilic disorders that may benefit from this treatment, and it could be a life-saving therapy. In this paper, we present two severe patients with eosinophil-induced diseases that had a good resolution after one dose of Benralizumab 30 mg. The first case is a severe non-necrotizing eosinophilic vasculitis following critical COVID-19 disease and the second case is a DRESS (Drug Rash with Eosinophilia and Systemic Symptoms Syndrome) due to allopurinol. Conclusions: The successful administration of Benralizumab in rare or severe eosinophilic disease could be an option for life-saving therapies when conventional treatments fail.

Immunological signature of chronic spontaneous urticaria (Review).

Chronic urticaria (CU) is a condition characterized by intensely pruritic, edematous, erythematous papules lasting for more than 6 weeks. Over half of the cases have concomitant swelling of deeper tissues, known as angioedema. The socio-economic burden of the disease is significant. Unfortunately, patients with severe CU, refractory to conventional treatment, have limited and expensive therapeutic options. The pathogenesis of CU is not yet completely understood. Therefore, elucidating the pathophysiological mechanisms involved would potentially identify new therapeutic targets. It has been accepted in recent years that mast cells and their activation, followed by excessive degranulation represent the key pathophysiological events in chronic spontaneous urticaria (CSU). The triggering events and the complexity of the effector mechanisms, however, remain intensely debated topics with conflicting studies. One pathogenetic mechanism incriminated in chronic spontaneous urticaria is the response mediated by the high-affinity receptor for IgE (FcεRI) expressed on mast cells. Increasing recognition of chronic spontaneous urticaria as an autoimmune disease linked to the cytokine-chemokine network imbalance resulting from alteration of innate immune response is another pathogenetic explanation. It is likely that these different pathological mechanisms are more interconnected, both acting synergistically, rather than separately, to produce the clinical expression of CU. The discovery and understanding of pathogenic mechanisms represent the premise for the development of safe and effective immunomodulators and targeted biological treatment for severe, refractory CU.

Predictive Factors for Oral Immune Modulation in Cow Milk Allergy.

Aim: The present study analyzed clinical and biological factors that might predict achievement of tolerance in patients with IgE-mediated cow milk allergy (CMA). Method: Seventy patients with IgE-mediated CMA (44.24 ± 24.16 months) were included in the study. The patients were evaluated clinically through skin prick test and sIgE to whole milk, casein, beta-lactoglobulin and alpha-lactalbumin. An eviction diet of 6 months was established, followed by oral food challenge test (OFC) and oral immunotherapy (OIT) with baked milk for 6 months. The tolerance was assessed after 2 years follow up. Results: Thirty percent of patients presented anaphylaxis of different degrees of severity as first manifestation of CMA. Sixty-two patients followed OIT or an accelerated reintroduction of milk. Ten patients (14.28%) did not obtain tolerance to milk within 2 years. A larger wheal in SPT and higher sIgE to milk, casein and betalactoglobulin were noted in patients with positive OFC. A basal level of <2.5 kU/l for sIgE to milk and <11.73 kU/l for sIgE to caseins predicted the occurrence of tolerance in patients with all types of clinical manifestations, including anaphylaxis. Conclusion: Basal levels of sIgE to milk and casein may help to identify patients that could become tolerant to milk.

COVID-19 Disease Leading to Chronic Spontaneous Urticaria Exacerbation: A Romanian Retrospective Study.

(1) Background: The COVID-19 pandemic has resulted in the exacerbation of various chronic diseases. Due to the potential impact of SARS-CoV-2 on mast cells, we aimed to analyze the relevance of COVID-19 disease on chronic spontaneous urticaria (CSU) clinical presentation and biological profile. (2) Methods: This study is a retrospective case series of patients with CSU diagnosed and treated in the Allergy Department of the Professor Doctor Octavian Fodor RIGH, (Cluj-Napoca, Romania). Patients were assessed for disease activity and level of control with the weekly urticaria activity score and the visual analogue scale. Results were correlated with COVID-19 severity and with nonspecific markers of inflammation during and after the SARS-CoV-2 infection. (3) Results: SARS-CoV-2 impacted a significant proportion (33%) of the CSU patients, of which 71% developed a moderate-severe form of COVID-19. Most of the patients (68%) had moderate-severe forms of CSU and 65% took AH1 treatment (one dose, two-fold dose or four-fold dose). The rest of them (35%) received the second-line treatment (40.3% Omalizumab, 53% Prednisolone and 4.8% Cyclosporine). In Omalizumab treated group of UCS patients we observed that COVID-19 disease was not severe. We established a positive correlation between the severity of the infection and that of the CSU clinical presentation, with most bothersome symptoms of urticaria being experienced by moderate to severe COVID-19 CSU patients (47%). Inflammatory markers were positively correlated (p = 0.01) with a more severe clinical profile of CSU, in accordance with our hypothesis that the level of inflammation triggered by COVID-19 disease has a role in CSU exacerbation. The non-specific inflammatory markers, such as CRP, were positively associated with the UAS7 score (R2 = 0.363; p = 0.001). An increased rate of exacerbation of CSU was observed in moderate-severe COVID-19 infection. (4) Conclusions: COVID-19 disease can result in the exacerbation of chronic spontaneous urticaria, more likely in moderate to severe forms of infection.

Hypersensitivity reactions to monoclonal antibodies: Classification and treatment approach (Review).

The present paper aims to review the topic of adverse reactions to biological agents, in terms of the incriminating mechanisms and therapeutic approach. As a result of immunomodulatory therapy, the last decade has achieved spectacular results in the targeted treatment of inflammatory, autoimmune, and neoplastic diseases, to name a few. The widespread use of biological agents is, however, associated with an increase in the number of observed adverse drug reactions ranging from local erythema to systemic reactions, including life-threatening immunologically mediated events, which justifies the need for a deeper understanding of this subject. Rapid desensitization to biological agents emerges as a treatment strategy for anaphylactic (immediate or delayed) hypersensitivity reactions as well as for severe infusion reactions. Drug desensitization is the administration of progressively increasing doses of the specific preparation until reaching the therapeutic dose in order to induce immunological tolerance and is indicated when the drugs are indispensable to the therapeutic regimen of individuals with hypersensitivity reactions to the preparation, with no reasonable alternatives.

Are Markers of Allergic Inflammation in Grass Pollen Allergy Influenced by H1 Antihistamines?

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum levels of ICAM-1 and VCAM-1 in patients with AR to grass pollen and their response to different H1 antihistamines. MATERIAL AND METHODS: A total of 50 patients with grass pollen AR were clinically and biologically evaluated. ICAM-1 and VCAM-1 serum levels were evaluated during pollen season before and after treatment with levocetirizine and desloratadine through the ELISA method. RESULTS: ICAM-1, VCAM-1, eosinophils, and total IgE were elevated in patients with AR, compared with healthy subjects. Both antihistamines improved specific symptoms of AR and increased patients' quality of life during pollen season after one month of treatment. H1 antihistamines reduced VCAM-1, ICAM-1, and total IgE after one-month treatment but not significantly. Patients with increased baseline values tend to remain with increased values after one-month AH1 treatment. CONCLUSIONS: ICAM-1 and sVCAM-1 levels are higher in patients with grass pollen-induced AR than healthy controls during pollen exposure. Their serum levels tend to remain at high values during pollen season despite antihistaminic therapy.