Uncaria Rhynchophylla and hirsuteine as TRPV1 agonists inducing channel desensitization.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (UR) is recognized for its therapeutic applications in treating hypertension and inflammation. However, the specific molecular mechanisms how UR and its bioactive constituents modulate inflammatory pathways remain unknown. This study investigates the effects of UR extract and its constituent, hirsuteine (HST), on TRPV1 channel modulation which is related to hypertension and inflammation. MATERIALS AND METHODS: Electrophysiological recordings and calcium imaging experiments were conducted to assess TRPV1 activation by UR extract and HST in HEK293T cells and sensory neurons. RESULTS: UR extract and HST activated TRPV1 in HEK293T cells, with repeated applications causing channel desensitization. HST application on TRPV1-positive sensory neurons significantly reduced electrical activity compared to capsaicin. CONCLUSION: This study demonstrated UR extract and HST are a novel TRPV1 agonists inducing channel desensitization and a potent agent for treatment of TRPV1 dependent pain relief.

Breaking the mold: nontraditional approaches to allergen immunotherapy for environmental allergens.

Allergen immunotherapy is a disease-modifying treatment for allergic diseases. The predominant traditional immunotherapy is through subcutaneous administration of allergens to gradually desensitize allergic individuals. While effective, traditional allergen immunotherapy approaches are often lengthy, time consuming for patients and can result in local or systemic adverse reactions. Nontraditional immunotherapies are emerging as promising alternatives, offering potentially more convenient, safe and efficacious treatment options. This review sought to comprehensively examine the safety, efficacy and performance of various nontraditional immunotherapies for environmental allergens. Nontraditional immunotherapy approaches covered in this review include sublingual, local nasal, intralymphatic rush and ultra-rush immunotherapy, allergoid, microbial and anti-IgE immunotherapies. Nontraditional immunotherapies show significant promise in addressing the limitations of traditional subcutaneous immunotherapy. Methods like intralymphatic and rush immunotherapy offer shorter treatment regimens, enhancing patient adherence and convenience. The co-administration of probiotics or monoclonal antibodies, like omalizumab, with AIT appears to improve treatment efficacy and safety. Despite these advancements, further large-scale, long-term studies are needed to establish standardized protocols, dosing and validate long-term effects of these nontraditional immunotherapies. Standardizing outcome measurements across studies is crucial for accurate comparisons of nontraditional immunotherapies prior to widespread clinical adoption of these innovative techniques.

Allergies occur when the body's immune system abnormally reacts to an allergen, which is a generally harmless substance such as pollen or dust. Allergen immunotherapy is a treatment for allergies that gradually decreases the body's immune response to the allergen by exposing patients to small doses of gradually increasing allergen. As a result, this treatment can prevent serious allergic reactions. Traditional immunotherapy called subcutaneous immunotherapy consists of regular injections over several years. This method is effective, but is inconvenient and can cause side effects. Newer nontraditional immunotherapy techniques have been developed, which include tablets under the tongue, nasal sprays, injections into lymph nodes, accelerated allergen delivery, modified allergen (allergoid) delivery and supplementing with probiotics and anti-IgE antibodies. These newer approaches improve convenience, safety and treatment timelines. However, existing studies on nontraditional immunotherapies have small sample sizes, unstandardized outcome measurements and inconsistent dosing protocols. As such, more research is needed for these nontraditional approaches before they can be widely used.

Conductance properties of the α9α10 nicotinic acetylcholine receptor of neonatal mouse inner and outer hair cells.

In the developing cochlea, just before the onset of hearing on postnatal day 12, the medial olivocochlear efferent axons in synaptic contact with the inner hair cells (IHCs) start withdrawing and new efferent synaptic connections are formed on the outer hair cells (OHCs), thereby progressing towards the adult pattern of medial olivocochlear efferent innervation. The synapses are inhibitory, calcium influx through the α9α10 nicotinic acetylcholine receptors (nAChRs) driving opening of calcium-dependent potassium channels. The nAChRs appear to function similarly in IHCs and OHCs, although with probable kinetic differences. Our aim was to assess their functional similarity in the neonatal mouse cochlea by making whole-cell recordings from both hair cell types between postnatal day 7 and 10 when nAChRs are expressed. ACh was applied to voltage-clamped hair cells by pressure-ejection from a pipette. The cells were dialysed with a Cs+-based solution designed to eliminate calcium-dependent potassium currents. There were differences in amplitude, voltage-sensitivity and reversal potential of the nAChR currents between IHCs and OHCs. There was also some indication that IHC nAChRs have slower activation and desensitization kinetics, although the relatively slow ACh application limited interpretation of this result. These differences, particularly concerning the reversal potential, might indicate the presence of different auxiliary protein subunits of the α9α10 receptor in neonatal IHCs and OHCs.

Anti-Plasma Cell Antibodies: A New Era of HLA Antibody Control in Solid Organ Transplantation?

New therapies directed against plasma cells such as anti-CD38 antibodies and the bispecific anti-BCMA antibodies, respresent not only an important advance in the treatment of multiple myeloma but have the potential to change the treatment landscape of other antibody-mediated diseases. In solid organ transplantation, the therapeutic armamentarium targeting humoral alloimmune responses in desensitization of highly sentized transplant candidates and post-transplant antibody mediated rejection has lagged behind advances in preventing and treating T cell-mediated rejection. IVIg and plasmapheresis are used extensively but have limited efficacy. Currently available anti-CD20 antibodies are only partially effective in achieving B cell depletion, and leave mature plama cells untouched. While interleukin 6 plays an important role in the humoral alloimmune response and injury, the benefits of IL-6 inhibitions have failed to be demonstrated in clinical trials. Even proteosome inhibitors developed specifically to target plasma cells have not fulfilled their promise, due to limited efficacy as single agents. This review focuses on the recent experience with, and potential applicability of, anti-CD38 antibodies in the field of organ transplantation and experimental data supporting their use and development for HLA desensitization and antibody-mediated rejection.

Digital transformation of mental health therapy by integrating digitalized cognitive behavioral therapy and eye movement desensitization and reprocessing.

Digital therapy has gained popularity in the mental health field because of its convenience and accessibility. One major benefit of digital therapy is its ability to address therapist shortages. Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that can develop after an individual experiences or witnesses a traumatic event. Digital therapy is an important resource for individuals with PTSD who may not have access to traditional in-person therapy. Cognitive behavioral therapy (CBT) and eye movement desensitization and reprocessing (EMDR) are two evidence-based psychotherapies that have shown efficacy in treating PTSD. This paper examines the mechanisms and clinical symptoms of PTSD as well as the principles and applications of CBT and EMDR. Additionally, the potential of digital therapy, including internet-based CBT, video conferencing-based therapy, and exposure therapy using augmented and virtual reality, is explored. This paper also discusses the engineering techniques employed in digital psychotherapy, such as emotion detection models and text analysis, for assessing patients' emotional states. Furthermore, it addresses the challenges faced in digital therapy, including regulatory issues, hardware limitations, privacy and security concerns, and effectiveness considerations. Overall, this paper provides a comprehensive overview of the current state of digital psychotherapy for PTSD treatment and highlights the opportunities and challenges in this rapidly evolving field.

Relevance of donor-specific HLA antibodies in hematopoietic cell transplantation.

Advances in hematopoietic cell transplantation have expanded the use of alternative donors such as haploidentical family donors or mismatched unrelated donors. However, donor-specific HLA antibodies (DSA) have been recognized as a significant risk factor of primary graft failure after HLA incompatible transplantation. Therefore, screening for HLA antibodies and taking DSA into consideration in the process of donor search play an increasingly important role in donor selection. If an HLA compatible donor is not available, desensitization may enable a successful transplantation. In this review, we describe the currently most widely used methods for HLA antibody detections including their pitfalls. In addition, we summarize the results of the studies on the impact of preformed DSA on transplant outcomes and their treatment options. Many more and larger studies are needed to clarify laboratory issues as well as immunological and clinical aspects in the management of DSA.

Quantification of Salivary Chromogranin A Levels during Routine Dental Procedures in Children: An In Vivo Study.

Background: Routine dental procedures frequently involve invasive treatment, multiple injections, and the use of sharp, high-speed cutting instruments, and treatment is often extended over several visits, which are said to be stress-provoking events. Salivary chromogranin A (CgA) is a biomarker that can help clinicians evaluate and quantify the stress experienced by a child during these procedures. Aim: To quantify the changes in salivary CgA levels in children before, during, and after routine dental procedures for multiple appointments. Materials and methods: Eight children, aged 6-8 years, visiting a clinic for the first time and requiring one class I restorative treatment and another treatment involving the use of local anesthesia were included in the study. Unstimulated salivary samples were collected from them during three visits-outpatient department (OPD), before, during, and after restorative treatment at the second visit, and before, during, and after treatment using local anesthesia in the third visit. The salivary samples were centrifuged, stored, and analyzed for CgA. Results: Salivary CgA levels showed a nonsignificant increase from 2.56 to 3.21 pmol/mg protein during the restorative treatment, followed by a nonsignificant reduction after cessation of the treatment. Whereas, salivary CgA levels before the use of local anesthesia were 1.88 pmol/mg protein, which showed a nonsignificant increase to 2.24 pmol/mg protein after its administration and progressed further to 3.27 pmol/mg protein even after the cessation of the treatment. Conclusion: The use of an airotor can cause an increase in stress levels in children, and local anesthesia administration is a more stress-provoking stimulus than an airotor. Multiple visits allow desensitization, which reduces stress and anxiety. Also, salivary CgA can be used as a reliable stress indicator in children. How to cite this article: Vora KM, Shah PP, Patil KV, et al. Quantification of Salivary Chromogranin A Levels during Routine Dental Procedures in Children: An In Vivo Study. Int J Clin Pediatr Dent 2024;17(5):585-590.

The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization.

The transient receptor potential vanilloid 1 (TRPV1) channel plays a dual role in peripheral neuropathic pain (NeuP) by acting as a "pain switch" through its sensitization and desensitization. Hyperalgesia, commonly resulting from tissue injury or inflammation, involves the sensitization of TRPV1 channels, which modulates sensory transmission from primary afferent nociceptors to spinal dorsal horn neurons. In chemotherapy-induced peripheral neuropathy (CIPN), TRPV1 is implicated in neuropathic pain mechanisms due to its interaction with ion channels, neurotransmitter signaling, and oxidative stress. Sensitization of TRPV1 in dorsal root ganglion neurons contributes to CIPN development, and inhibition of TRPV1 channels can reduce chemotherapy-induced mechanical hypersensitivity. In diabetic peripheral neuropathy (DPN), TRPV1 is involved in pain modulation through pathways including reactive oxygen species and cytokine production. TRPV1's interaction with TRPA1 channels further influences chronic pain onset and progression. Therapeutically, capsaicin, a TRPV1 agonist, can induce analgesia through receptor desensitization, while TRPV1 antagonists and siRNA targeting TRPV1 show promise in preclinical studies. Cannabinoid modulation of TRPV1 provides another potential pathway for alleviating neuropathic pain. This review summarizes recent preclinical research on TRPV1 in association with peripheral NeuP.

Omalizumab Implementation in Practice: Lessons Learned from the OUtMATCH Study.

In February 2024, omalizumab was approved by the Food and Drug Administration for the treatment of food allergy, based on data from the landmark Phase 3 clinical trial "Omalizumab as Monotherapy and as Adjunct Therapy in Children and Adults (OUtMATCH)." In this Rostrum, OUtMATCH investigators share their perspectives on the trial results, the implications for translation into daily practice, and on remaining gaps in the field. The study met its primary and key secondary endpoints, demonstrating a large effect size in multi-allergen desensitization compared to placebo; yet there were some participants who did not respond, and the percentage of responders tolerating all 3 food allergens was lower than that for single foods. . Clinicians are likely to have many questions about appropriate patient selection, monitoring for treatment responsiveness, and how to manage off-label considerations such as dietary incorporation or co-treatment with oral immunotherapy. Additional research is needed to answer these remaining questions and ensure that the translation of omalizumab in real-world practice leads to high-quality outcomes.

Omalizumab reduces anaphylactic reactions and allows food introduction in food-allergic in children with severe asthma: An observational study.

BACKGROUND: In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA). OBJECTIVE: We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat. METHODS: Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels. RESULTS: In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50. CONCLUSIONS: During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT06316414.

Impact of immunoglobulin preparations on anti-HLA antibody specificity analysis.

BACKGROUND: Donor-specific antibodies (DSAs) targeting human leukocyte antigens (HLAs) substantially reduce the longevity of transplanted organs. Desensitization of DSA-positive renal transplant recipients is achieved through intravenous administration of immunoglobulin (IVIg). However, the presence and detectability of anti-HLA antibodies in IVIg preparations following administration are not fully understood. We aimed to assess whether immunoglobulin preparations contain anti-HLA antibodies that can be detected as passive antibodies when administered into the body. METHODS: We evaluated 3 immunoglobulin preparations from different pharmaceutical companies, using anti-HLA class I and II antibody specificity tests and immunocomplex capture fluorescence analysis (ICFA). RESULTS: Direct testing for anti-HLA antibodies resulted in high background errors, particularly for Venoglobulin. Diluting Venoglobulin to physiological concentrations revealed the presence of anti-HLA class I antibodies; however, no common alleles were found between the specificity identification test and ICFA.For Glovenin and Venilon, anti-HLA class I and II antibodies were detected; however, variability was observed across different test reagent lots. Moreover, dilution of the globulin formulation revealed a prozone phenomenon. CONCLUSION: The administration of IVIg complicates the accurate detection of anti-HLA antibodies, underscoring the need for careful interpretation of test results post-IVIg administration.

Single center experience with more than 600 drug desensitization in Colombia.

Background: Drug hypersensitivity reactions (DHRs) have a significant impact on both, patient and their treating physicians; it is considered a public health concern. The history of allergy to drugs, limits therapeutic options and will lead to the use of more expensive and potentially less effective options. Drug desensitization (DD) is considered as a procedure with a positive impact on the prognosis of the patient's disease. The objective of this study is to describe the experience with a substantial number of drugs desensitization in a fourth level center in Cali, Colombia. Methods: An observational, cross-sectional and descriptive study was conducted. Patients with DHRs who underwent a standardized institutional DD protocol, between March of 2012 and May of 2023, were included. Results: Two hundred forty-one patients were included. The median age was 47.8 years (4-88). One hundred fifty-six (64.7%) were women, including three who were pregnant. A total of 641 DDs were performed. The most frequent groups of drugs for which the desensitization was performed were monoclonal antibodies in 83 patients (34.4%), chemotherapeutic agents in 53 (21.6%), NSAIDs in 44 (18.2%), and antibiotics in 42 (17.4%). Eighty-seven patients (36.1%) experienced hypersensitivity to the culprit drug on first exposure, while 154 (63.9%) exhibited reactions during subsequent cycles. The main clinical presentation that gave rise to desensitization was anaphylaxis in 125 patients (51.8%), followed by cutaneous symptoms in 106 patients (44%). The predominant observed endophenotype was type 1 in 188 patients (78.3%), followed by mixed type in 46 patients (19.2%). Breakthrough reactions were observed in 50 patients (20.7%). Tolerance to DD was achieved in 636 of the procedures (99.2%), allowing the continuity of treatment of choice for the underlying disease. Conclusions: Most desensitized patients were women with type I reactions. Monoclonal antibodies were the most frequent culprit drugs. DD in patients with DHRs is a useful, safe and effective procedure. The administration of the implicated drug had a positive impact on the course of the disease in these patients.

Successful desensitization to etoposide in a patient after cardiac arrest.

INTRODUCTION: Etoposide phosphate is a chemotherapeutic agent used to treat various malignant neoplasms. Hypersensitivity reactions may occur with its use, and in rare cases, an anaphylactic reaction can manifest. Available options for patients experiencing hypersensitivity reactions include premedication, changing treatment, or undergoing desensitization. Various pediatric desensitization protocols have been described, ranging from six to fifteen steps, while published adult cases are rare. CASE REPORT: We report the case of a 61-year-old woman with small-cell lung cancer and brain metastases. In November 2019, she underwent the second cycle of cisplatin and etoposide phosphate treatment. While receiving etoposide phosphate, she experienced dyspnea and suffered a cardiorespiratory arrest, leading to cardiopulmonary resuscitation and subsequent admission to the Intensive Care Unit. Her acute tryptase levels were notably elevated at 18 µg/L (compared to a baseline tryptase level of 6,6 µg/L) during the reaction. CASE MANAGEMENT: We implemented a 16-step desensitization protocol (without premedication) under close monitoring in an intermediate care unit. The protocol was successfully executed over three cycles until tumor progression mandated a modification in systemic treatment. DISCUSSION: To our knowledge, this is the first documented case of successful desensitization to etoposide phosphate in a patient who experienced cardiac arrest during a hypersensitivity reaction. Although protocols of varying lengths have been published, we emphasize the importance of individualizing each protocol to fit the severity of the reaction and the resources and experience of each unit.

Lidocaine-saturated cotton tip applicator used for laryngeal desensitization resulting in an iatrogenic tracheobronchial foreign body in two cats.

Case series summary: Two cats were referred to a veterinary teaching hospital with a cotton tip applicator (CTA) tracheobronchial foreign body (FB) after induction of anesthesia for an elective dental cleaning. In both cases, a lidocaine-saturated CTA, utilized to desensitize the larynx before endotracheal (ET) intubation, broke when introduced into the oropharynx and was subsequently aspirated into the tracheobronchial tree. Both CTAs were successfully removed bronchoscopically, and the cats survived with no short- or long-term complications noted. Relevance and novel information: Utilizing a lidocaine-saturated CTA to facilitate ET intubation in cats is not well described, and information on the relative risks and benefits of this specific method for laryngeal desensitization is lacking. This retrospective case series is the first to describe a complication of this technique and successful treatment. These cases highlight the risk inherent to using a CTA to desensitize the feline larynx.

The effect of allergen immunotherapy in patients with central compartment atopic disease post-surgery.

OBJECTIVE: To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post-surgery. METHODS: A retrospective cohort of surgically treated, HDM-sensitized CRSwNP patients phenotyped as CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use (<4 times/week vs. ≥4 times/week, %) and the rhinologic domain of the 22-item sino-nasal outcome test (SNOT-22). Demographic characteristics, concomitant asthma, smoking status, history of aspirin-exacerbated respiratory disease, conjunctival symptoms, polysensitization, serum eosinophils (cell × 109/L), tissue eosinophilia (% > 100/HPF), and serum IgE (kU/L) were also recorded. RESULTS: Eighty-six CCAD patients were assessed (41 ± 14 yrs, 64% female). AIT was applied in 37% (n = 32). Baseline features were similar apart from greater conjunctival symptoms (72 vs. 45%, p = 0.02) in the AIT group. At 12 months post-surgery, the AIT group has less MT edema (% ≥ diffuse 15.6 vs. 52.9, p < 0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (% ≥ 4/week, 37.5 vs. 79.6%, p < 0.01). The rhinologic symptoms were similar (21.1 ± 17.1 vs. 20.1 ± 21.6, p = 0.83). CONCLUSIONS: Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de-escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation.

The Efficacy of Eye Movement Desensitization and Reprocessing Treatment for Depression: A Meta-Analysis and Meta-Regression of Randomized Controlled Trials.

Background: Eye Movement Desensitization and Reprocessing (EMDR) therapy has gained attention for its potential effectiveness in treating depression beyond its initial use for PTSD. This systematic review and meta-analysis aims to evaluate the efficacy of EMDR in treating depression and to identify the variables influencing its effectiveness. Methods: A comprehensive search was conducted across databases, including MEDLINE, PubMed, and EMBASE, covering studies up to January 2023. A total of 521 studies were screened, and 25 studies with 1042 participants (522 EMDR, 520 control) met the inclusion criteria and were included in the meta-analysis. The inclusion criteria involved randomized controlled trials (RCTs) comparing EMDR to control conditions such as usual care or waitlist groups, with outcomes focused on changes in depression symptoms. Results: The results show that EMDR had a significant effect on reducing depression symptoms (Hedges' g = 0.75), with moderate heterogeneity being observed. The meta-regression indicated that the severity of depression was a significant predictor of EMDR's effectiveness, with greater effects in severe cases. Additionally, the systematic review analyzed and evaluated various theoretical models and related studies that explain how EMDR works for the treatment of depression, reporting on neurobiological models proposed in previous research. Conclusions: This study confirms that EMDR is effective in treating depression, particularly in severe cases, and highlights its potential as a non-pharmacological intervention. However, this study highlights the need for more standardized research and long-term evaluations to assess EMDR's lasting impact. Integrating EMDR into multimodal treatment plans and primary care, especially for treatment-resistant depression, could significantly improve patient outcomes.

Current Goals of NSAID-ERD Management: Patient-Centered Approaches Involving NSAID Desensitization With and Without Biologics.

The classic approach of nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NSAID-ERD) includes pharmaceutical and surgical treatments, as well as avoidance of cyclooxygenase 1-inhibitor NSAIDs. The introduction of biologics in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps represents an alternative therapeutic approach to the classical aspirin therapy after desensitization (ATAD) in some regions, and with convincing results. However, their use is limited due to approval and/or high-cost restrictions. NSAID-ERD is a mainly type 2 and highly eosinophilic disease, and mAbs targeting IgE or IL-5, IL-4, and IL-13 have been shown to be effective for both severe asthma and severe chronic rhinosinusitis with nasal polyps. So far, dupilumab demonstrated greater efficacy in patients with NSAID-ERD than in aspirin-tolerant patients with regard to several clinical outcomes. Patients with NSAID-ERD respond very rapidly to omalizumab also, with reduction in the release of prostaglandin D2 and cysteinyl leukotrienes. Patients favored biologic treatment over ATAD in multiple retrospective analyses, which must be acknowledged when choosing one or the other option. Although this review will summarize ATAD in general, it will more prominently focus on when ATAD should be considered, even when type 2 biologics are available. In addition, there are conflicting studies as to whether patients on a type 2 biologic become desensitized to NSAIDs, because omalizumab proved to restore tolerance to aspirin in only two-third of patients. This goal of NSAID tolerance should be considered as part of disease control future approaches, representing one of many aspects in a patient-centered care approach.

Successful desensitization to atezolizumab-induced near-fatal anaphylaxis in patients with hepatocellular carcinoma: A case report and literature review.

Atezolizumab, a humanized antiprogrammed death ligand 1 monoclonal immunoglobulin G1 antibody, is a targeted therapeutic drug known as an immune checkpoint inhibitor. It is currently used to treat various types of cancer, including unresectable hepatocellular carcinoma (HCC), nonsmall cell lung cancer, urothelial cancer, and breast cancer, and is becoming a therapeutic option in the forefront of oncology treatment. However, it may sometimes lead to undesirable adverse reactions owing to the activation of immune responses in various organs. Cutaneous adverse reactions to atezolizumab are well known; however, cases of anaphylaxis are very rare. In this report, we present the first case of HCC who experienced near-fatal anaphylaxis to atezolizumab in South Korea.

Platelet Aggregation Alterations in Patients with Severe Viral Infection Treated at the Intensive Care Unit: Implications for Mortality Risk.

Severe viral infections often result in abnormal platelet function, affecting various stages of hemostasis. Activated platelets are often considered prothrombotic and more susceptible to further stimulation. However, emerging evidence suggests that initial hyperactivation is followed by platelet exhaustion and hypo-responsiveness, affecting platelet degranulation, activation, and aggregation. We examined early alterations in platelet aggregation among patients (N = 28) with acute respiratory distress syndrome and SARS-CoV-2 infection who were receiving mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Blood samples were stimulated with four different activators: arachidonic acid, adenosine diphosphate, thrombin receptor-activating protein 6, and ristocetin. Our observations revealed that platelet aggregation was reduced in most patients upon admission (ranging from 61 to 89%, depending on the agonist used), and this trend intensified during the 5-day observation period. Concurrently, other coagulation parameters remained within normal ranges, except for elevated d-dimer and fibrinogen levels. Importantly, we found a significant association between platelet aggregation and patient mortality. Impaired platelet aggregation was more severe in patients who ultimately died, and reduced aggregation was associated with a significantly lower probability of survival, as confirmed by Kaplan-Meier analysis (p = 0.028). These findings underscore the potential of aggregometry as an early detection tool for identifying patients at higher risk of mortality within this specific cohort.