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Objective Design Setting Animals Interventions Results Conclusions To evaluate the safety of repeated administration of a lyophilized canine‐specific albumin (CSA) product and to quantify its effect on serum albumin concentrations and colloid osmotic pressure (COP) in healthy dogs.Prospective study.University research facility.Six healthy, adult, purpose‐bred Beagles.Dogs received 1 g/kg of 16% CSA intravenously on days 1, 2, and 14 and were observed, with serial measurement of vital parameters during and for 2 hours after each infusion, to monitor for adverse events or evidence of a hypersensitivity reaction. Serum albumin concentration and COP were measured at predetermined time points before and after each infusion.One dog experienced a single episode of vomiting approximately 1 hour after completion of the second infusion. No other adverse reactions were observed during the 28‐day study period. Serum albumin concentration was increased by a mean of 0.57 g/dL (5.7 g/L) (P = 0.003) when measured 2 hours after the first CSA infusion, and albumin concentration remained significantly higher than baseline at 24 hours after infusion, with a mean difference of 0.42 g/dL (4.2 g/dL) (P < 0.001). The second and third CSA infusions similarly increased serum albumin concentration at 2 hours (P = 0.001 and P = 0.001, respectively) and 24 hours (P = 0.012 and P = 0.007, respectively) after infusion. COP increased by a mean of 2.03 mm Hg at 2 hours after the first infusion (P = 0.013) and remained significantly higher than baseline at 24 hours after infusion, with a mean difference of 1.52 mm Hg (P = 0.002). The second CSA infusion similarly increased COP at 2 hours (P < 0.001) and 24 hours (P = 0.017) after infusion. The third CSA infusion increased COP at 2 hours after infusion (P = 0.004) but did not achieve statistical significance at 24 hours after infusion (P = 0.053).A 1‐g/kg dose of lyophilized CSA was effective at increasing serum albumin concentration and COP. Repeated infusions of CSA appear safe in healthy dogs. [ABSTRACT FROM AUTHOR]

Paclitaxel is one of the first-line treatments for breast, ovarian, and lung cancers. However, its use is limited by the high frequency of hypersensitivity reactions. In this retrospective chart review at Memorial Sloan Kettering Cancer Center, we assess clinical factors associated with immediate and delayed hypersensitivity reactions to paclitaxel and characterize delayed hypersensitivity reactions to paclitaxel in patients with breast cancer. 12,274 patients were treated with paclitaxel. 6,165 had breast cancer and 1,233 were seen by a dermatologist. 734 patients (11.9%) developed an immediate hypersensitivity reaction. Age (p < 0.001), race (p < 0.001), and prior history of allergy (p = 0.05) were associated with immediate hypersensitivity reactions. 147 patients (4.0%) had a rash of interest. The most common phenotypes were maculopapular (52%) and urticaria (36%). Race (p < 0.001) and history of allergy (p < 0.001) were associated with development of a cutaneous reaction. Patients with an immediate hypersensitivity reaction were more likely to have developed a delayed cutaneous reaction (OR = 1.80). Risk factors for development of immediate hypersensitivity reactions in this study were younger age, race, and history of allergy. Patients who developed an immediate hypersensitivity reaction were more likely to develop a delayed hypersensitivity reaction. Risk factors for development of the rash included Asian race and history of allergy. Identification of risk factors is critical to guide care coordination. Awareness of these clinical factors which are associated with development of a rash could guide providers in choosing treatment with paclitaxel or nab-paclitaxel. If the cutaneous reactions are bothersome to the patient, the transition of treatment from paclitaxel to nab-paclitaxel may be warranted, or a consideration of re-challenge or desensitization may be discussed. [ABSTRACT FROM AUTHOR]

Human recombinant enzyme replacement therapy, given to compensate for genetic enzyme deficiency in lysosomal storage diseases, delays the progression of the disease and improves the quality of life. However, enzyme replacement therapy may cause hypersensitivity reactions. Within the scope of this research, we aimed to elucidate the frequency and clinical features of hypersensitivity reactions against enzyme replacement therapy in children with lysosomal storage diseases and clarify the management of these reactions. Medical records of pediatric patients with lysosomal storage disease and receiving enzyme replacement therapy were retrospectively reviewed, and patients who experienced allergic reactions were included in the study. The demographic characteristics of the patients, their diagnosis, the responsible enzyme, the time at which the reaction started and at what dose, the signs and symptoms associated with the reaction, diagnostic tests, the management of the reaction, and the protocol applied for the maintenance of enzyme replacement therapy after the reaction were recorded. Hypersensitivity reactions developed in 18 of 71 patients (25.3 %) who received enzyme replacement therapy. The most common cutaneous findings were observed. Anaphylaxis developed in 6 of 18 patients. Patients who experienced recurrent hypersensitivity reactions with premedication or a slower infusion rate, those with positive skin test results, and patients who developed anaphylaxis were given enzyme replacement therapy with desensitization. HSR may develop during enzyme replacement therapy, which are vital in lysosomal storage diseases, and discontinuation of enzyme replacement therapy is a significant loss for patients with metabolic disorders. These reactions can be treated with premedication and long-term infusions, but some patients may require desensitization protocols for continued treatment. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper is to report the case of a patient who developed a local allergic reaction to the pigment used for permanent eyebrow makeup. In addition, the authors' protocol for the treatment of such a complication is proposed. Methods: A patient visited the clinic to remove permanent eyebrow makeup. In the patient's opinion, the eyebrows were too dark and incorrectly shaped. Upon physical examination of the brows, they were found to be over-pigmented and drawn outside the area of hair growth of the natural brow. Results: The patient underwent 24 treatment procedures to remove the pigmentation including four sessions of laser therapy and subsequent treatments using a chemical substance (remover). No adverse effects occurred during the initial phase of makeup removal (black pigment removal), but an allergic reaction appeared with the removal of the red-orange colored pigment (after the fourth laser therapy session). The following symptoms appeared: redness, swelling, and the appearance of papules filled with both serous fluid and pigment used for the permanent makeup. After each remover treatment, the allergic reaction decreased, and local symptoms gradually subsided. Additionally, topical corticosteroid treatment was implemented peri-procedurally. The patient's case suggests a secondary allergic reaction to the red-orange pigment used for permanent makeup. Conclusions: The literature on this topic is scarce; therefore, we present a regimen for the management of such complications. In addition, we draw attention to the fact that allergic reactions to pigment may not always occur immediately following skin pigmentation but may become apparent long after the procedure, such as when the allergen is "exposed" during an attempt to remove or correct the makeup. [ABSTRACT FROM AUTHOR]

Since 2011, indocyanine green (ICG) has been increasingly used in surgery as a diagnostic tool. Although allergic reactions to this fluorescent dye are considered rare, they can result in anaphylactic shock. We report the case of a 33-year-old woman who developed anaphylaxis immediately after ICG administration during laparoscopic-assisted high anterior resection. The patient was treated with intravenous adrenaline, and the surgery continued. Elevated plasma histamine and serum tryptase levels immediately after ICG administration and intradermal testing identified ICG as the causative agent. The frequency of ICG use is increasing, and anesthesiologists should recognize ICG as a prevalent perioperative allergen.

Background Hypersensitivity reaction is a rare side effect during immunosuppressive treatment with azathioprine (AZA). Some cases of cardiac involvement have already been reported but causality is notoriously difficult to prove. Case summary We present the case of a 68-year-old man with two episodes of reversible left ventricular (LV) dysfunction. One month after treatment initiation with AZA, he developed non-specific symptoms, including mild chest pain. In the context of elevated cardiac biomarkers and markers of inflammation, echocardiography showed depressed systolic LV function. Biventricular dysfunction was shown on cardiac magnetic resonance imaging (CMR), but neither myocardial oedema nor late gadolinium enhancement was documented. There was full recovery of LV function after AZA discontinuation. Very similar clinical course and echocardiography findings were observed early after restarting AZA treatment. After definitive cessation of AZA, systolic LV function recovered again and remained stable throughout long-term follow-up. Discussion Hypersensitivity reaction with cardiac involvement due to AZA is rare. The exact mechanisms underlying AZA-related cardiac dysfunction are still not completely understood, and causality is often difficult to prove. However, because of re-exposure to the drug, which, considered retrospectively, was inappropriate, the effect was clearly apparent in our patient. Knowledge of this potentially life-threatening side effect of AZA treatment is important. AZA must be discontinued promptly if there is any evidence of hypersensitivity reaction. [ABSTRACT FROM AUTHOR]

Introduction: Platinum-based chemotherapy is the mainstay of first-line therapy for advanced-stage non-small cell lung cancer (NSCLC). Although carboplatin-induced hypersensitivity reactions (HSRs) commonly occur following multiple cycles of therapy, they are rarely observed during the first cycle of the treatment. Case report: Here, we report the case of a 70-year-old man with advanced-stage NSCLC who developed HSR possibly caused by carboplatin during the first cycle of induction with platinum-doublet chemotherapy plus pembrolizumab. The patient presented with bronchial obstruction due to a centrally located tumor. No driver mutations were detected, and the programmed death-ligand 1 expression ranged from 1% to 24%. Consequently, the patient was treated with pembrolizumab combined with carboplatin and paclitaxel. However, immediately after the start of carboplatin, the blood pressure and oxygen levels of the patient dropped and he began exhibiting an altered level of consciousness. These findings indicated carboplatin-induced anaphylaxis. Hypotension and oxygen desaturation improved following carboplatin discontinuation and normal saline administration. Management and outcome: The basophil activation test for both carboplatin and cisplatin was negative. Thus, the risk of anaphylaxis owing to both drugs was ruled out, and carboplatin was believed to have induced grade 3 HSR. Subsequently, carboplatin-based chemotherapy was switched to cisplatin-based chemotherapy. HSR was not observed during the four treatment cycles with pembrolizumab, cisplatin, and pemetrexed, and best response was partial response. Discussion: Cisplatin-based chemotherapy could be used as an alternate treatment in patients with NSCLC who develop severe carboplatin-induced HSR. [ABSTRACT FROM AUTHOR]

Yang Zhao,1 Hua Wang,2 Zhengjun Wu,1 Yunxiang Zhu,1 Jingsong Wang1 1Department of Pharmacy, Guangyuan Central Hospital, Guangyuan, Sichuan, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jingsong Wang, Department of Pharmacy, Guangyuan Central Hospital, Guangyuan, Sichuan, People’s Republic of China, Email wjs5515@163.comBackground: Adverse reactions induced by isoosmolar contrast medium (iodixanol) are mostly mild, with rashes and headaches being the most common. Although anaphylactic shock has been reported, no related incidents have been documented on cerebral angiography.Objective: This article reports a serious case of anaphylactic shock possibly induced by iodixanol and provides an overview of the case report.Case Summary: A 65-year-old female with persistent headaches for nearly six months and CTA examination revealed multiple intracranial aneurysms. After two treatments, she returned to the hospital for aneurysm of reexamination a month ago. Following a preoperative assessment, cerebral angiography was performed. Three minutes after the procedure, the patient experienced dizziness, increased heart rate, followed by hypotension (BP 90/43 mm Hg), a sudden drop-in heart rate (HR 68 bpm), and a drop in SpO2 to 92%. Intravenous dexamethasone for anti-allergic were administered immediately, along with therapy through oxygen-inhalation. However, the patient then developed limb convulsions, unresponsiveness, and was urgently given diazepam for sedation and sputum aspiration to maintain airway patency. Blood pressure decrease to 53/29 mm Hg, and SpO2 readings were unavailable. Intravenous dopamine to elevates blood pressure, and assists breathing by intubating in the endotracheal. After 3 minutes, as the blood pressure remained undetectable, intermittent intravenous epinephrine 1mg was administered to raise the blood pressure, gradually restoring it to 126/90 mm Hg, and SpO2 increased to 95%. The patient was diagnosed with iodixanol-induced anaphylactic shock and urgently transferred to the NICU for monitoring and treatment. The patient died despite immediate treatment.Conclusion: A 65-year-old female developed serious anaphylactic shock during cerebral angiography after receiving iodixanol. Although iodixanol is considered one of the safest iodinated contrast mediums (ICM), clinicians should be aware of its the potential for serious hypersensitivity reactions that can lead to fatal and life-threatening events.Keywords: iodixanol, cerebral angiography, hypersensitivity reaction, anaphylactic shock

Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR. We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated. From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX. IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics. What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation. What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity. How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug. [ABSTRACT FROM AUTHOR]

Contrast media (CM)-associated adverse effects including mainly acute kidney injury and hypersensitivity reactions still remain a significant treatment burden to vulnerable patients requiring percutaneous coronary intervention (PCI). The complete omission of CM administration accompanied by intravascular ultrasound (IVUS) guidance may offer an appropriate revascularization treatment. We hereby present a case series of four patients with challenging coronary lesions and relative/absolute contraindications to CM use [(hypersensitivity reaction owning to CM, history of contrast-induced acute kidney injury, solitary kidney, or advanced chronic kidney disease (CKD)] who underwent absolute zero-contrast IVUS-guided PCI following a predetermined protocol. The initial diagnostic angiography was reviewed for landmark identification, and multiple guidewires created a metallic road map providing additional landmarks and protected side branches. IVUS imaging was performed to determine lesion length, reference segments and landing zones, assess stent expansion/apposition and identify major complications. All procedures were successfully completed without any CM administration, renal function deterioration, pericardial effusion, or stent edge dissection. We demonstrated the feasibility of absolute zero-contrast IVUS-guided PCI in patients with complex coronary lesions susceptible to CM-associated adverse effects. Since the safety of this strategy is well-documented in patients with CKD and challenging lesions morphology even in acute settings, evidence-based validation of this approach is capable of changing the otherwise conservative treatment of vulnerable patients where even minimum doses of CM may have detrimental effects. Patients with vulnerable renal function as well as former hypersensitivity reaction to contrast media encounter a significant treatment burden regarding coronary artery disease. Zero-contrast IVUS-guided strategy based on a predetermined protocol provides a feasible alternative approach in patients susceptible to contrast media-associated adverse effects even in the presence of complex coronary lesions. • CM side effects (renal function impairment and hypersensitivity reactions) are a treatment burden to vulnerable patients. • The complete omission of CM during PCI with the advent of IVUS may be the answer to CM-associated adverse effects. • Zero-contrast IVUS-guided strategy based on a predetermined protocol is a feasible approach even in complex coronary lesions. • A randomized multicenter control trial will examine the effectiveness of this technique and its clinical significance. [ABSTRACT FROM AUTHOR]

To determine whether updated guidance by the ACR in 2017 advocating use of intravenous (IV) premedication in emergency department (ED) patients and inpatients with reported iodinated contrast allergy was associated with a change in clinical practice. An anonymous survey was distributed via e-mail in October 2020 to practicing radiologist members of the ACR interrogating use of corticosteroid premedication for two clinical vignettes: an indicated routine (perform within 24 hours) inpatient contrast-enhanced CT (CE-CT) and an indicated urgent (perform within 6 hours) ED CE-CT. In both scenarios, the patient had a prior moderate hypersensitivity reaction to iodinated contrast media. Clinical management was evaluated. Data were compared to historical controls from 2009. The response rate was 11% (724 of 6,616). For the inpatient scenario, 72% (518 of 724) would use corticosteroid premedication with CE-CT, and 28% (200 of 724) would perform noncontrast CT. For the ED scenario, 67% (487 of 724) would use corticosteroid premedication with CE-CT, and 30% (217 of 724) would perform noncontrast CT. Oral premedication (85%, 439 of 518) was preferred for routine inpatients, and rapid IV premedication (89%, 433 of 487) was preferred for urgent ED patients. Of those who provided rapid IV dosing data in the ED, two doses of corticosteroids were used by 53% (216 of 410) and one dose was used by 45% (185 of 410), with academic radiologists more likely than private or hybrid practice radiologists to administer two doses (74% [74 of 100] versus 48% [151 of 312], P <.001, odds ratio, 3.03; 95% confidence interval, 1.84-5.00). Rapid IV premedication was more commonly used in 2020 than in 2009 (60% [433 of 724] versus 29% [20 of 69], P <.001, odds ratio, 3.65; 95% confidence interval, 2.12-6.26). Antihistamine use was common in both inpatient (93%, 480 of 518) and ED settings (92%, 447 of 487). Only 32% (229 of 721) of radiologists practiced in accordance with ACR guidelines, suggesting no need for routine premedication before CE-CT in patients with prior severe hypersensitivity reaction to gadolinium-based contrast media. Nonetheless, most (93%, 670 of 724) said the ACR Manual on Contrast Media was a major determinant of their practice. Use of rapid IV premedication in urgent settings has increased since 2009, following updated ACR guidelines, but there is disagreement over whether one or two corticosteroid doses is required. Despite reported high reliance on ACR guidelines, deviations from those guidelines remain common. In general, when ACR guidelines were not followed, it was in a risk-averse direction. [Display omitted] [ABSTRACT FROM AUTHOR]

Paclitaxel hypersensitivity reactions (HSRs) are prevalent, especially in females. The common paclitaxel pretreatment, dexamethasone, may inhibit chemotherapy efficacy and accelerate tumor progression. We aimed to balance paclitaxel HSRs and the lowest dexamethasone dose for gynecologic malignancies. We retrospectively examined 1,074 cycles of 3-weekly paclitaxel-containing treatment for 231 gynecologic malignancies at Xiangya Hospital. HSR incidence with different dexamethasone regimens was the primary outcome. Risk factors were examined in all cycles using univariate and multivariate models with generalized estimating equations. A subgroup analysis of initial exposure to paclitaxel was also conducted. HSR occurred in 33 patients (14.29%) and 49 cycles (4.56%), including 69.39% in cycles 1–2. There were no severe HSRs (grade ≥3). Different premedication regimens, including dexamethasone dosage and route, ranitidine presence or absence, didn't affect HSR incidence in univariate and multivariate analyzes (p > 0.05). Premenopausal women exerted fewer HSRs (ORadj 0.22, 95%CI 0.08–0.58; p = 0.002). At the first exposure to paclitaxel, more than 10 mg of dexamethasone didn't diminish HSRs (OR 0.83, 95%CI 0.27–2.59; p = 0.753). In gynecologic malignancies, 10 mg dexamethasone along with 20 mg diphenhydramine may be adequate to prevent paclitaxel HSRs without ranitidine. It is necessary to reevaluate paclitaxel premedication regimens. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) filler, a transient injectable used for rejuvenating facial treatments, has become increasingly popular over time since it doesn’t require surgery. Although these procedures are generally safe, there are some application-related complications. These issues fall into three categories: reactions with early, delayed, or late onset. This case report features a 55-yearold female patient who developed widespread facial edema as a result of a delayed hypersensitivity reaction that happened after HA filler was applied. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions (DHRs) to platinum-based compounds (PCs) are on the rise, and their personalized and safe management is essential to enable first-line treatment for these cancer patients. This study aimed to evaluate the usefulness of the basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PCs. A total of 24 patients with DHRs to PCs (20 oxaliplatin and four carboplatin) were evaluated: thirteen patients were diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients were diagnosed as non-allergic with negative STs and DPTs, and five patients were classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. The BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarray were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control groups were negative for sIgE- and BAT-microarray. Our experience indicated that the sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PCs and may provide an advance in decision making for drug provocation testing. [ABSTRACT FROM AUTHOR]

Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Cross-reactivity between related NSAIDs in FDE has been reported, but among chemically unrelated NSAIDs, is rare. Herein, we present a rare well-documented case where a patient initially displayed tolerance to etoricoxib after experiencing a nimesulide-induced FDE. Subsequently, the patient developed an etoricoxib-induced FDE, accompanied by the development of bullous lesions. This case report and the literature review on comparable FDE occurrences shed light on the intricate nature of FDEs, suggesting the possibility of cross-reactivity between chemically related and unrelated NSAIDs or the emergence of new drug-specific T cells without cross-reactivity after multiple exposures to a drug in a susceptible patient. Our case underscores the importance of increased awareness and vigilance among both physicians and patients in the realm of personalized medicine. Further research is needed to unravel the intricate mechanisms behind these drug eruptions, improve diagnostic approaches, and enhance patient care. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypersensitivity reactions (HSRs) to platinum and taxane are common, and desensitization can be used to complete the standard chemotherapy regimen with a good safety profile and high success rate. Our study showed that the use of desensitization for HSRs to taxane and platinum is low in clinical practice. Treatment of HSRs has been shown to be heterogeneous and dependent on the grade of the HSR. Guidelines for the treatment of HSRs to taxane and platinum in gynecologic cancers have been of great interest to clinicians. Our study highlights that the management of platinum and taxane HSRs in gynecological cancers could be standardized and that international guidelines need to be developed. Platinum and taxane chemotherapy is associated with the risk of hypersensitivity reactions (HSRs), which may require switching to less effective treatments. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen. Therefore, we aimed to investigate the current management of HSRs to platinum and/or taxane chemotherapy in patients with gynecologic cancers. We conducted an online cross-sectional survey among gynecological and medical oncologists consisting of 33 questions. A total of 144 respondents completed the survey, and 133 respondents were included in the final analysis. Most participants were gynecologic oncologists (43.6%) and medical oncologists (33.8%), and 77.4% (n = 103) were involved in chemotherapy treatment. More than 73% of participants experienced >5 HSRs to platinum and taxane per year. Premedication and a new attempt with platinum or taxane chemotherapy were used in 84.8% and 92.5% of Grade 1–2 HSRs to platinum and taxane, respectively. In contrast, desensitization was used in 49.4% and 41.8% of Grade 3–4 HSRs to platinum and taxane, respectively. Most participants strongly emphasized the need to standardize the management of platinum and taxane HSRs in gynecologic cancer. Our study showed that HSRs in gynecologic cancer are common, but management is variable and the use of desensitization is low. In addition, the need for guidance on the management of platinum- and taxane-induced HSRs in gynecologic cancer was highlighted. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well‐known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%–3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence‐based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in‐depth investigations in the topic. [ABSTRACT FROM AUTHOR]

Background: In case of suspected hypersensitivity reactions (HRs) to drugs, a challenging area for pediatricians is detecting relevant elements in the parent‐reported history, in order to reach a definite diagnosis. We analyzed the concordance between the description of the HR and the medical reports documented at the time of the event. Furthermore, we studied any correlation between clinical history variables and the prediction of true allergy. Methods: We retrospectively collected 50 charts of children referred to our Allergy Unit, after a previous access to the Emergency Department. We compared the description of the HR at acute phase to the history told by parents. Type and timing of the HR and culprit drug were classified as "known" or "unknown." The diagnosis was confirmed or excluded at the end of the investigations. Logistic regression analysis was performed to find any significant association. Results: The type of the HR was known in 74%, the timing in 28%, and the culprit drug in 98%. We showed that having had a severe HR had an increased odds of remembering the timing; being older >6 years and having had an immediate HR had an increased odds of remembering the type; time to diagnostic was lower in patients whose parents remembered the type of HR. Conclusion: Our paper underlines the importance of an accurate anamnesis at the time of the event. Providing the physicians with a standardized Case Report Form could be a useful tool to simplify the diagnostic work‐up and minimize mistakes due to lack of memory. [ABSTRACT FROM AUTHOR]

Introduction: Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. Methods: Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. Results: This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre‐existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620–18,282) mg, and the mean number of doses was 14 (4–63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. Conclusion: Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider. [ABSTRACT FROM AUTHOR]

Drug-induced anaphylaxis in children is less common than in adults and primarily involves beta-lactams and nonsteroidal anti-inflammatory drugs. Epidemiological studies show variable prevalence, influenced by age, gender, and atopic diseases. The pathophysiology includes IgE-mediated reactions and non-IgE mechanisms, like cytokine release reactions. We address drug-induced anaphylaxis in children, focusing on antibiotics, nonsteroidal anti-inflammatory drugs, neuromuscular blocking agents, and monoclonal antibodies. Diagnosis combines clinical criteria with in vitro, in vivo, and drug provocation tests. The immediate management of acute anaphylaxis primarily involves the use of adrenaline, coupled with long-term strategies, such as allergen avoidance and patient education. Desensitization protocols are crucial for children allergic to essential medications, particularly antibiotics and chemotherapy agents. [ABSTRACT FROM AUTHOR]

Introduction: Patients with platinum resistant epithelial ovarian cancer have limited treatment options which are further limited by hypersensitivity reactions to first line medications such as paclitaxel. Paclitaxel is a taxane that inhibits microtubules and has a high incidence of hypersensitivity reactions. Mirvetuximab soravtansine-gynx (MIRV) is a folate receptor alpha (FRα) directed antibody and microtubule inhibitor that is approved for patients with FRα positive platinum resistant recurrent epithelial ovarian cancer. Both medications are microtubule-targeting agents with similar binding sites, therefore a theoretical risk of cross reactivity between paclitaxel and MIRV may exist. Additionally, phase II clinical trial, SORAYA, did not include data on patients with prior hypersensitivity to paclitaxel. Case: This is the case of a 33-year-old female with recurrent stage IIIC epithelial ovarian cancer with a history of severe anaphylaxis to paclitaxel. She was deemed eligible for MIRV after progression on multiple regimens, but MIRV was given with caution given her severe reaction history. With proper pre-treatment and monitoring, she was treated with MIRV without a reaction. Discussion: It is suspected that most paclitaxel reactions are due to the cremophor solvent rather than paclitaxel itself; however, cross reactivity with docetaxel which is suspended in a polysorbate solution can also occur. Therefore, there is no clear way to determine the risk of cross reactivity between paclitaxel and similar medications. MIRV is also suspended in polysorbate and has a similar mechanism to taxanes, therefore it was unknown if a patient with a prior grade 5 reaction to paclitaxel would also have a reaction to MIRV. Though this is one case, patients with a history of severe hypersensitivity to paclitaxel and meet the criteria for MIRV could be treated with MIRV with careful monitoring.

Introduction. Kounis syndrome (KS) represents an acute coronary syndrome (ACS) induced by a hypersensitivity reaction. First described by Kounis and Zavras in 1991, KS today represents an infrequently diagnosed clinical syndrome. Three different KS variants have been defined: type I vasospastic allergic angina, type II allergic myocardial infarction, and type III stent thrombosis. Outlines of cases. This paper presents three cases of type II KS causing anaphylactic ACS. In the first case, a 66-year-old female presented with dyspnea, dizziness, and electrocardiography findings suggesting ACS after she was stung by a bee. In the second case, we present a 64-year-old female admitted to the Emergency Department with chest pain after an anaphylactic reaction due to an iodine contrast injection used for a thoracic computed tomography scan. In the third case, an 80-year-old female presented with chest pain, palpitation, and skin rash shortly after administration of the intravenous anesthetic propofol during elective malignant colon tumor surgical intervention. All patients were treated at the Cardiology Clinic, University Clinical Center of Serbia. Conclusion. The primary mechanism of KS corresponds to the release of inflammatory mediators during a hypersensitivity reaction triggered by different sources. Although well known, constant reminders of this cause of ACS are needed.

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. [ABSTRACT FROM AUTHOR]

Delayed hypersensitivity reactions (DHRs) have been reported in association with COVID-19 vaccines, particularly those that are mRNA-based. Classic DHRs result in induration, erythema, tenderness, and urticaria. However, soft tissue mass is an uncommon complication of a COVID-19 vaccination-associated DHR and is rarely reported in the literature. We present a case of a 49-year-old male who recognized a mildly painful, firm soft tissue mass within the biceps mimicking neoplasm six months after receiving the booster dose of the Moderna vaccine. Non-operative conservative treatment modalities, including heating pads, ice packs, acetaminophen, and ibuprofen, failed to improve the patient's mass. The mass, which proved histologically to be an inflammatory pseudo-tumor, did not recur after complete excision. While there have been many reported cases of DHRs following COVID-19 vaccinations, we present this case to raise awareness of the development of pseudo-tumors as a possible, yet rare, clinical manifestation of DHRs following vaccination. [ABSTRACT FROM AUTHOR]

Background: Exposure to paclitaxel and carboplatin has the risk of developing hypersensitivity reactions (HSRs), which could necessitate using less effective treatments to avoid anaphylaxis. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen; therefore, this study investigated rates and benefits of successful desensitization in patients with gynecologic cancers (GC). Methods: We collected data from 241 patients with GC who had at least one cycle of platinum or taxane chemotherapy. The rate of HSRs and successful desensitization were evaluated, and an outcome analysis was conducted. Results: The rate of HSRs to platinum and taxane was 6.39% and 13.07%, respectively. We observed a 100% success rate of desensitization in our cohort. Patients with HSR were significantly younger (57.1 vs. 64.9 years, p=0.030) in the taxane cohort. Importantly, the overall survival (OS) of patients with platinum and taxane HSRs who underwent desensitization was comparable to that of patients with no HSRs (platinum vs. controls; median OS 60.36 vs. 60.39months, p=0.31; taxane vs. controls; OS 80.29 vs. 60.00months, p=0.59). Conclusion: Thus, we show that desensitization for platinum and taxane HSRs is safe and effective, resulting in an outcome that is well comparable to patients without HSR. Based on these observations, desensitization procedures might be considered as standard of care before switching to less effective treatment for patients with GC. [ABSTRACT FROM AUTHOR]

Immune-mediated acute coronary syndrome, also known as Kounis syndrome (KS), is an underrecognized and challenging diagnosis. In this case report, we present a case of cardiac arrest secondary to iodinated contrast allergy requiring emergent cardiac catheterization and hemodynamic support secondary to type 2 KS. KS necessitates a high index of clinical suspicion by the treating physician in order to address both the hypersensitivity reaction and its cardiac implications. Kounis syndrome (KS) is a clinically distinct entity from anaphylaxis; managing KS in the same way as anaphylaxis can worsen cardiac demand and ischemia. In addition, KS may present as coronary vasospasm or plaque rupture; regardless, percutaneous coronary intervention (PCI) should be performed as worse outcomes have been described in cases where PCI is not performed or delayed. [ABSTRACT FROM AUTHOR]

Rocuronium, a nondepolarizing neuromuscular blocking agent used for muscle relaxation especially during endotracheal intubation, can cause hypersensitivity reactions. This article provides an overview of anaphylactic reactions; risk factors; and the pathophysiology, presentation, diagnosis, treatment, and nursing implications associated with rocuronium‐induced anaphylaxis. Life‐threatening anaphylaxis can be immunoglobulin E–mediated or non–immunoglobulin E‐mediated and usually occurs after the first dose. Anaphylaxis can present with hypotension and bronchospasm; cutaneal symptoms, such as erythema, may not be obvious. Diagnosis is initially presumptive and may require a transesophageal echocardiogram to rule out other causes of hypotension (eg, pulmonary embolus). Emergency treatment begins with epinephrine administration and fluid boluses; cardiac support devices may be needed. Definitive diagnosis requires early measurement of histamine and tryptase levels and skin testing after the patient recovers from the reaction. Perioperative nurses should be prepared to participate in emergency treatment of anaphylaxis and advocate for testing for a definitive diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Introduction Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. Methods Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. Results This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre‐existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620–18,282) mg, and the mean number of doses was 14 (4–63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. Conclusion Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

ABSTRACT Although rarely reported in veterinary medicine, this article shows three cases of dogs that presented anaphylactic reactions after intravenous administration of meloxicam at therapeutic doses. Three dogs of different breeds and ages were submitted to anesthesia for surgical procedures of ovariohysterectomy and repair of patellar luxation. The animals were classified as ASA I and did not present changes in clinical and laboratory tests. All dogs were anesthetized and monitored by anesthesiologists, with careful multiparametric evaluation. Near the end of the procedures, meloxicam was administered intravenously in all dogs, and the drug used had the same commercial presentation and concentration, but with different lot numbers and with different months. For less than a minute, the animals showed significant hypotension, with pressure values close to 30 mmHg or inaudible by Doppler. The animals had no skin signs, only hypotension and a decrease in heart rate in one of them. All dogs were immediately treated with intravenous ephedrine and atropine in the bradycardic patient. After the emergency treatment, the dogs showed stabilized vital signs, with no complications or need for additional intervention. After the event, the three dogs showed no signs of clinical, behavioral or laboratory changes.

Breast cancer is one of the most common malignancies, with a 10-year survival rate for early non-metastatic stages of over 80%. However, recurrence or relapse may occur decades after completing therapy, and cancer survivors have also a risk of secondary neoplasia especially due to radiation therapy. This case highlights the challenges of an accurate diagnosis and appropriate treatment in patients with second primary cancer and uncommon metastasis.

Abstract Background Exposure to paclitaxel and carboplatin has the risk of developing hypersensitivity reactions (HSRs), which could necessitate using less effective treatments to avoid anaphylaxis. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen; therefore, this study investigated rates and benefits of successful desensitization in patients with gynecologic cancers (GC). Methods We collected data from 241 patients with GC who had at least one cycle of platinum or taxane chemotherapy. The rate of HSRs and successful desensitization were evaluated, and an outcome analysis was conducted. Results The rate of HSRs to platinum and taxane was 6.39% and 13.07%, respectively. We observed a 100% success rate of desensitization in our cohort. Patients with HSR were significantly younger (57.1 vs. 64.9 years, p = 0.030) in the taxane cohort. Importantly, the overall survival (OS) of patients with platinum and taxane HSRs who underwent desensitization was comparable to that of patients with no HSRs (platinum vs. controls; median OS 60.36 vs. 60.39 months, p = 0.31; taxane vs. controls; OS 80.29 vs. 60.00 months, p = 0.59). Conclusion Thus, we show that desensitization for platinum and taxane HSRs is safe and effective, resulting in an outcome that is well comparable to patients without HSR. Based on these observations, desensitization procedures might be considered as standard of care before switching to less effective treatment for patients with GC.

Introduction: Kounis Syndrome was first described in 1991 by Kounis and Zavras as “the concurrence of chest pain during an allergic reaction, accompanied by clinical laboratory findings of classical angina pectoris caused by inflammatory mediators released during the allergic insult” [1]. The mechanism of Kounis Syndrome most likely involves the release of cytokines through mast-cell degranulation, which leads to coronary vasospasm and atheromatous plaque erosion or rupture following the allergic reaction to an allergen.[2] The treatment is specific to acute coronary syndrome and anaphylaxis, with the added complication that the drugs used, while indicated in each of the two disorders separately, may present contradictions when administered jointly in one patient.[3] The purpose of this review is to briefly revise the existing literature regarding its overlooked diagnosis and contradictory joint management of anaphylaxis and acute coronary syndrome. We will conduct a brief review of the current literature on Kounis Syndrome while describing a suspected case of a female patient presented with both anaphylaxis symptoms and angina pectoris. Conclusions: Kounis syndrome is defined as the co-incidental occurrence of an acute coronary syndrome with hypersensitivity reactions following an allergic reaction. Treatment of allergic reactions may be sufficient in type I KS. In contrast, coronary intervention is needed in the other two types, accompanied by vasodilator drugs, including nitrates and calcium antagonists, each of which may have contradictory effects.

Bacterial spot of tomato and chili pepper, caused by four species of Xanthomonas and various races, is one of the diseases with the greatest impact on horticulture worldwide. The aim of this study was to identify the species and physiological races of Xanthomonas present in tomato (Solanum lycopersicum) and chili pepper (Capsicum annuum) crops in Sinaloa, Mexico. For this purpose, samples with typical symptoms of bacterial spot were collected in commercial fields of the different municipalities in the state of Sinaloa. Ninety-three bacteria were isolated on semi-selective medium as nutrient agar and yeast extract-dextrose. A total of 47 bacteria were identified as Xanthomonas by a combination of morphological, pathogenic, biochemical, physiological, and molecular tests. In addition, to characterize the morphological race of each strain, differential tomato (four) and chili pepper (six) lines were used. Molecular diagnostic using specific primers indicated that 83% corresponded to X. euvesicatoria, 10.6% to X. perforans, and 6.4% to X. vesicatoria. At the physiological race level, races T1, T2, T3, and T5 were detected in tomato; while the Xanthomonas races detected in chili pepper were P0, P3, P6, P8 and P10. This information updates previous data on the distribution of races of Xanthomonas that infect chili peppers in Sinaloa, since races P6 and P10 are reported for the first time. [ABSTRACT FROM AUTHOR]

Ferric carboxymaltose (FCM) is a non-dextran iron preparation used for intravenous treatment of iron deficiency anaemia (IDA) in adult patients with intolerance or poor response to oral iron therapy. Acute hypersensitivity reactions (HSRs) during iron infusions are very rare but can be life-threatening even after receiving a prior test dose. Here, we report a case of 42 years old female patient who underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy. On the next postoperative day she received an injection of ferric carboxy maltose. She was diagnosed with IDA. She presented with the picture of an adverse drug reaction due to injection FCM. She was managed with oxygen, vasopressors, antihistaminics, intravenous fluids and, corticosteroids. She recovered well within 24 hours of intensive care unit admission following this adverse drug reaction. So, careful and precise observation is required in management of adverse reaction following ferric carboxymaltose and prompt recognition and treatment based on severity is warranted.

Hyaluronic acid filler, a temporary injectable used for rejuvenating facial treatments, has gained significant popularity over the years due to its nonsurgical approach. While these procedures are generally safe, there are certain complications associated with their application. These complications can be categorized into early-, delayed-, and late-onset reactions. In this case report, we present a 55-year-old female who experienced a delayed hypersensitivity reaction following the application of hyaluronic acid filler, resulting in generalized facial edema.

Vaccine-associated adverse events (VAAEs), including feline injection-site sarcomas (FISSs), occur only rarely but can be severe. Understanding potential VAAEs is an important part of informed owner consent for vaccination. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of feline medicine experts, presents the current knowledge on VAAEs in cats, summarizing the literature and filling the gaps where scientific studies are missing with expert opinion to assist veterinarians in adopting the best vaccination practice. VAAEs are caused by an aberrant innate or adaptive immune reaction, excessive local reactions at the inoculation site, an error in administration, or failure in the manufacturing process. FISS, the most severe VAAE, can develop after vaccinations or injection of other substances. Although the most widely accepted hypothesis is that chronic inflammation triggers malignant transformation, the pathogenesis of FISS is not yet fully understood. No injectable vaccine is risk-free, and therefore, vaccination should be performed as often as necessary, but as infrequently as possible. Vaccines should be brought to room temperature prior to administration and injected at sites in which FISS surgery would likely be curative; the interscapular region should be avoided. Post-vaccinal monitoring is essential. [ABSTRACT FROM AUTHOR]

Background: Paclitaxel is a chemotherapeutic agent used in the treatment of multiple types of malignant tumors which was discovered from the Taxus brevofilia tree. In some patients, anaphylaxis develops during the first exposure to paclitaxel, suggesting that primary sensitization may have occurred through hidden or unidentified allergens that produce cross-reactivity. Skin testing may be useful in identifying sensitization to these allergens. Atopy has also been reported in patients with hypersensitivity reactions (HSR) to paclitaxel. The aim of this study is to evaluate the association between atopy and sensitization to allergens with the development of immediate HSR to paclitaxel. Methods: Skin prick tests (SPT) for environmental and food allergens were applied to 76 patients recently diagnosed with cancer. A SPT to paclitaxel was applied and if negative, an intradermal test was performed. After paclitaxel's infusion, the development of immediate HSR was observed. Results: Of 76 skin tests, 43% of patients had allergen sensitization and 57% did not. HSR occurred in 12.1% and 11.6% of each group, respectively. Five percent of patients tested positive to paclitaxel and only one had an immediate HSR. Eighty-nine percent of patients who developed an HSR had a family or personal history of atopy. Conclusions: Sensitization to environmental or food allergens does not appear to be a risk factor for the development of immediate HSR to paclitaxel, suggesting that there are other non-IgE-mediated immunologic mechanisms responsible for their development, however, a personal and family history of atopy increases 8x the risk of developing anaphylaxis. [ABSTRACT FROM AUTHOR]

Lysosomal storage diseases (LSDs) are rare genetic metabolic disorders that cause the accumulation of glycosaminoglycans in lysosomes due to enzyme deficiency or reduced function. Enzyme replacement therapy (ERT) represents the gold standard treatment, but hypersensitivity reaction can occur resulting in treatment discontinuation. Thus, desensitization procedures for different culprit recombinant enzymes can be performed to restore ERT. We searched desensitization procedures performed in LSDs and focused on skin test results, protocols and premedication performed, and breakthrough reactions occurred during infusions. Fifty‐two patients have been subjected to desensitization procedures successfully. Skin tests, with the culprit recombinant enzyme, deemed positive in 29 cases, doubtful in two cases, and not performed in four patients. Moreover, 29 of the 52 desensitization protocols used at the first infusion were breakthrough reaction free. Different desensitization strategies have proved safe and effective in restoring ERT in patients with previous hypersensitivity reactions. Most of these events seem to be Type I hypersensitivity reactions (IgE‐mediated). Standardized in vivo and in vitro testing is necessary to better estimate the risk of the procedure and find the safest individualized desensitization protocol. [ABSTRACT FROM AUTHOR]

Currently, in the dark coniferous forests of the Baikal region, the spread of the disease bacterial wetwood disease is noted, causing the sanitary condition deterioration in the forest stands, and leading to the forest dieback on large territories. Despite the fact that this disease has been known since the beginning of the last century, the question of its’ real pathogen is still open. It is believed that associations of various endophytic microorganisms may take part in the development of pathogenesis. In this regard, it seems relevant to study the composition of the endophytic complex of microorganisms in wood with bacterial wetwood of forest species in order to establish the types of relationships between endophytes and test their ability to initiate a pathological process in conifers. An attempt was made to identify the main endophytic microbiome representatives of the «wet wood» of Siberian stone pine (Pinus sibirica Du Tour) affected by bacterial wetwood, to assess their phytopathogenic properties and types of relationships between them. The features of the endophytic microbiome of the Siberian stone pine affected by bacterial wetwood in the Slyudyanskoye forestry of the Irkutsk region were studied. With standard microbiological and phytopathological methods we isolated pure cultures of bacteria and studied their characteristics (including virulence). For bacterias identification molecular genetic methods were used. From the infested wood of Siberian stone pine trees affected by bacterial wetwood, a complex of pure microorganisms cultures, not previously described in other studies, was isolated. Among them, opportunistic strains include Rouxiella chamberiensis, Ewingella americana, Stenotrophomonas rhizophila and Bacillus pumilus, which exhibit pronounced virulent properties in relation to indicator plants and ambiguously affect the growth and development of Scotch pine (Pinus sylvestris L.) seedlings. Mutual impacts of bacteria on each other were noted in the endophytic microbiome of the affected Siberian stone pine wood. Bacillus bacteria showed pronounced antagonistic properties. Basically, in the endophytic community symbiotic relationships were dominated with possible syntrophic connections.

Immune-checkpoint inhibitors (ICIs) are the most effective treatments nowadays. Nivolumab was the second ICI used for treating solid tumors with amazing results. Patients treated with Nivolumab may react differently to this treatment. Some people tolerate this treatment very well without experiencing any adverse reactions, whilst some may have mild symptoms and a part of them can present severe reactions. In our research, we sought to identify the answers to four questions: 1. what type of cancer has more severe hypersensitivity reactions to Nivolumab, 2. what is the time frame for developing these severe reactions to Nivolumab, 3. whether it is best to continue or stop the treatment after a severe hypersensitivity reaction to Nivolumab and 4. what severe hypersensitivity reactions are the most frequent reported along Nivolumab treatment. This review also highlights another problem with regard to the usage of concomitant and prior medications or other methods of treatment (e.g., radiation therapy), which can also lead to severe reactions. Treatment with Nivolumab is very well tolerated, but patients should also be warned of the possibility of severe hypersensitivity reactions for which they should urgently see a doctor for a personalized evaluation. There are some options for individuals with severe hypersensitivity reactions, for eg. switching the medication or applying a desensitization protocol.