Oral calcium supplementation versus placebo in mitigating citrate reactions during apheresis: an open-label randomized control trial.

BACKGROUND: Citrate-related hypocalcemia is the most common adverse event linked with peripheral blood progenitor cell apheresis. A previous retrospective study highlighted the prophylactic effectiveness of oral calcium drinks before apheresis, supplemented with intravenous calcium gluconate. Consequently, this study is a randomized controlled trial comparing oral calcium with placebo drinks STUDY DESIGN AND METHODS: Healthy donors were randomized to receive either oral calcium (Cohort A) or placebo (Cohort B) drinks. If symptoms emerged, all donors were given calcium drinks to counteract hypocalcemia. The primary endpoint centered on the incidence of Grade 1 or higher citrate-related symptoms. Analyses were performed using the crude model and doubly robust estimation. RESULTS: Forty-two healthy donors participated from January 2021 to July 2022. Case distribution (Cohort A: Cohort B) stood at 3:7 (Grade 1), 2:2 (Grade 2), and 1:0 (Grade 3); no Grade 4 cases were identified. There was no statistical significance in the incidence of Grade 1 or higher and Grade 3 citrate-related symptoms. DISCUSSION: The cumulative incidence of citrate-related side effects was less pronounced than in the previous research. This could stem from absence of blinding, and the decision to administer calcium drinks to the untreated group upon symptom detection. Although preemptive oral calcium intake before peripheral blood progenitor cell apheresis is not wholly effective, providing calcium-rich beverages to symptomatic donors may stave off symptom intensification.

Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

OBJECTIVES: Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. METHODS: In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed. RESULTS: In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. CONCLUSIONS: The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Focused Ultrasound in Cancer Immunotherapy: A Review of Mechanisms and Applications.

Ultrasound is well-perceived for its diagnostic application. Meanwhile, ultrasound, especially focused ultrasound (FUS), has also demonstrated therapeutic capabilities, such as thermal tissue ablation, hyperthermia, and mechanical tissue ablation, making it a viable therapeutic approach for cancer treatment. Cancer immunotherapy is an emerging cancer treatment approach that boosts the immune system to fight cancer, and it has also exhibited enhanced effectiveness in treating previously considered untreatable conditions. Currently, cancer immunotherapy is regarded as one of the four pillars of cancer treatment because it has fewer adverse effects than radiation and chemotherapy. In recent years, the unique capabilities of FUS in ablating tumors, regulating the immune system, and enhancing anti-tumor responses have resulted in a new field of research known as FUS-induced/assisted cancer immunotherapy. In this work, we provide a comprehensive overview of this new research field by introducing the basics of focused ultrasound and cancer immunotherapy and providing the state-of-the-art applications of FUS in cancer immunotherapy: the mechanisms and preclinical and clinical studies. This review aims to offer the scientific community a reliable reference to the exciting field of FUS-induced/assisted cancer immunotherapy, hoping to foster the further development of related technology and expand its medical applications.

Energy-Based Device Management of Nodular Reaction Following Poly-D, L-Lactic Acid Injection for Tear Trough Rejuvenation.

BACKGROUND: Poly-D,L-lactic acid (PDLLA) is used for tear trough rejuvenation but can cause complications like nodular reactions. This report describes using a radiofrequency device to manage these nodules. CASE PRESENTATION: A 42-year-old woman developed firm, non-inflammatory nodules 3 weeks after receiving PDLLA (Juvelook) injections in the tear trough area. The nodules were firm and not associated with erythema or tenderness. INTERVENTION: The monopolar radiofrequency device was used directly on the nodules with 150 shots at an energy level 115 J, 28.75 J/cm². The treatment resulted in complete resolution of the nodules within 24 hours. RESULTS: The radiofrequency treatment effectively resolved the nodular reaction without recurrence, highlighting the device's compatibility with the unique structure of Juvelook's PDLLA. CONCLUSION: Radiofrequency therapy is effective for managing nodular reactions following PDLLA injections. Further research is needed to optimise protocols and improve the safety of biostimulator treatments in cosmetic procedures.

Clinical and radiological pattern of olaparib-induced interstitial lung disease.

BACKGROUND: PARP inhibitors (PARPi) are used in the treatment of ovarian, breast, pancreatic, and prostate cancers. Pneumonitis has been identified as a potential side effect, with a higher meta-analysis-assessed risk for olaparib versus other PARPi. Olaparib-induced interstitial lung disease (O-ILD) was first described within the Japanese population, with few information available for Caucasian patients. METHODS: We performed a retrospective study by pooling data from the French and Belgian pharmacovigilance databases from 2018 to 2022. Patients with O-ILD were included following a central review by: 1) pharmacologists using the French drug causality assessment method; 2) senior pneumologists or radiologists, using the Fleischner Society's recommendations. RESULTS: Five patients were identified and analysed. All were females, with ovarian or breast cancer. Median age at O-ILD diagnosis was 71 (38-72) years old, with no smoking history. Median delay between treatment initiation and symptom occurrence was 12 (6-33) weeks. Pneumonitis severity assessed using the Common Terminology Criteria for Adverse Events V5 was Grade 3 (n = 4) or 2 (n = 1). CT-scan review (n = 3) described hypersensitivity pneumonitis reaction as a common pattern. Bronchioalveolar lavage (n = 4) revealed lymphocytic alveolitis. Treatments relied on olaparib discontinuation (n = 5) and glucocorticoid intake (n = 4), with no fatal issue. Safe re-challenge with PARPi occurred in two patients. Forty additional O-ILD cases were identified in the WHO VigiBase database, including one fatal case. CONCLUSIONS: PARPi-ILD is a rare but potentially life-threatening disease, presenting as a hypersensitivity pneumonitis pattern within 3 months of PARPi initiation. Treatment primarily relies on medication discontinuation. Re-challenging with another PARPi could be considered. CLINICAL TRIAL NUMBER: CEPRO #2023-010.

Assessing the effect of high-dose rosuvastatin in elderly patients over 75 with acute coronary syndrome.

BACKGROUNDS AND OBJECTIVE: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are pivotal in managing hypercholesterolemia and reducing cardiovascular risk. While rosuvastatin demonstrates superior efficacy and tolerability compared to other statins, its safety profile in elderly patients older than 75 years old with acute coronary syndrome (ACS) remains underexplored. So, the objective of this study is to evaluate the frequency of adverse reactions and investigate the efficacy of high-dose rosuvastatin on lipid profiles in elderly patients aged over 75 with ACS. METHODS: In this observational study, 110 consecutive elderly ACS patients attending Modarres Hospital in Tehran, Iran, in 2019 were enrolled. The effects of high-dose rosuvastatin were assessed in elderly patients older than 75 years old by comparison of the adverse effects, lipid profile, cardiac function, and other biomarkers at the baseline and after 6 weeks of rosuvastatin therapy with a dose of 40 mg. RESULTS: Following 6 weeks of treatment, there was a significant reduction in total cholesterol (136.2 ± 24.3 to 115.5 ± 24.0, p = 0.001) and LDL levels (72.6 ± 17.5 to 50.9 ± 18.9, p = 0.001), accompanied by a notable increase in HDL levels (38.3 ± 7.1 to 47.2 ± 7.4, p = 0.001). Cardiac function, as measured by ejection fraction (EF), significantly improved from 43.4 ± 8.8 to 48.5 ± 8.5 (p = 0.001). Adverse effects such as cramps (N = 12, p = 0.001), weakness (N = 28, p = 0.001), and anorexia (N = 12, p = 0.001) were reported but did not warrant discontinuation of therapy. Notably, no cases of jaundice were observed. Two deaths occurred due to major adverse cardiac events (MACE) during the study period, unrelated to stroke or recurrent myocardial infarction. CONCLUSION: Totally, high-dose rosuvastatin therapy effectively improved lipid profiles, cardiac function, and liver enzyme levels in elderly ACS patients, with manageable adverse effects. These findings underscore the importance of rosuvastatin in optimizing cardiovascular health in this vulnerable population.

The subchronic toxicity of higher olefins in Han Wistar rats.

Higher olefins (HO) are a category of unsaturated hydrocarbons widely used in industry applications to make products essential for daily human life. Establishing safe exposure limits requires a solid data matrix that facilitates understanding of their toxicological profile. This in turn allows for data to be read across to other members of the category, which are structurally similar and have predictable physico-chemical properties. Five independent subchronic oral toxicity studies were conducted in Wistar rats with Oct-1-ene, Nonene, branched, Octadec-1-ene, Octadecene and hydrocarbon C12-30, olefin-rich, ethylene polymn. by product, at doses ranging from 20 to 1000 mg/kg bw. These HO were selected considering gut absorption, carbon chain length, double-bond position and carbon backbone structural variations. Generally, limited and non-adverse toxicity effects were observed at the end of the treatment for short carbon chain HO. For instance, alpha 2u-globulin nephropathy in the male rats and liver hypertrophy. No clear trend in systemic toxicity was linked to the double-bond position. Key factors for hazard assessment include absorption, carbon chain length, and branching, with Nonene, branched, identified as the worst-case substance. Taken together, the no observed adverse effect level (NOAEL) of each HO in these subchronic studies was set at the highest dose tested.

Granulomatous hyperinflammatory state induced by dupilumab treatment for eosinophilic esophagitis.

We present the first case of a dupilumab-induced hyperinflammatory state in the setting of underlying eosinophilic esophagitis characterized by multisystem granulomatous inflammation. Although clinical trial data and subsequent real-world experience support dupilumab as a highly effective therapy for eosinophilic esophagitis, close monitoring for development of adverse symptoms following initiation remains paramount.

Inflammation related to inhalation of nano and micron sized iron oxides: a systematic review.

Inhalation exposure to iron oxide occurs in many workplaces and respirable aerosols occur during thermal processes (e.g. welding, casting) or during abrasion of iron and steel products (e.g. cutting, grinding, machining, polishing, sanding) or during handling of iron oxide pigments. There is limited evidence of adverse effects in humans specifically linked to inhalation of iron oxides. This contrasts to oxides of other metals used to alloy or for coating of steel and iron of which several have been classified as being hazardous by international and national agencies. Such metal oxides are often present in the air at workplaces. In general, iron oxides might therefore be regarded as low-toxicity, low-solubility (LTLS) particles, and are often considered to be nontoxic even if very high and prolonged inhalation exposures might result in diseases. In animal studies, such exposures lead to cancer, fibrosis and other diseases. Our hypothesis was that pulmonary-workplace exposure during manufacture and handling of SPION preparations might be harmful. We therefore conducted a systematic review of the relevant literature to understand how iron oxides deposited in the lung are related to acute and subchronic pulmonary inflammation. We included one human and several in vivo animal studies published up to February 2023. We found 25 relevant studies that were useful for deriving occupational exposure limits (OEL) for iron oxides based on an inflammatory reaction. Our review of the scientific literature indicates that lowering of health-based occupational exposure limits might be considered.

Atezolizumab-Induced Ulcerative Colitis in Patient with Hepatocellular Carcinoma: Case Report and Literature Review.

Background and Objectives: Immune check inhibitor (ICI) colitis is one of most common and adverse side effects of ICI. However, there was no case report of ulcerative colitis (UC)-mimicking colitis after atezolizumab use in hepatocellular carcinoma (HCC) to our knowledge. Materials and Methods: We would like to introduce the case of a patient with Stage IV HCC who complained of abdominal pain, diarrhea and rectal bleeding after two cycles of atezolizumab/bevacizumab chemotherapy and was then diagnosed with UC-mimicking colitis. Results: Endoscopy revealed typical findings of UC, suggesting diagnosis of UC-mimicking colitis. The patient was treated with systemic steroids and oral mesalamine, which significantly improved his symptoms, which were also supported by endoscopic findings. The patient resumed chemotherapy with atezolizumab and bevacizumab without any interruption to the chemotherapy schedule. Conclusions: Early endoscopic evaluation is pivotal to diagnosing UC-mimicking colitis. If diagnosed, UC-based treatments such as steroids and mesalamine should be strongly considered. Given previous reports of inflammatory bowel disease (IBD) flare-ups after immunotherapy, routine lower endoscopy, performed together with upper endoscopy before atezolizumab/bevacizumab therapy, is promising to patients.

Effect of the BiZact™ Low-Temperature Dissecting Device on Intra- and Postoperative Morbidities Related to Tonsillectomy-A Systematic Review and Meta-Analysis.

Background and Objectives: We investigated the effects of using a BiZact™ device for tonsillectomy on operating time, intraoperative blood loss, postoperative bleeding rate, and pain through a meta-analysis of the relevant literature. Materials and Methods: We reviewed studies retrieved from the databases of PubMed, SCOPUS, Google Scholar, Embase, Web of Science, and Cochrane up to March 2024. The results were analyzed following PRISMA guidelines. Six studies that compared the outcomes of patients receiving perioperative BiZact™ tonsillectomy with those in control groups (cold steel dissection or bipolar tonsillectomy) were included for this analysis of the outcomes, which included intraoperative bleeding and time, postoperative pain, and frequency of postoperative bleeding. Results: The operative time (SMD -11.5985, 95%CI [-20.3326; -2.8644], I2 = 99.5%) in the treatment group was significantly reduced compared to the control group. However, BiZact™ showed no significant efficacy in reducing intraoperative bleeding when compared with the control group (SMD -0.0480, 95%CI [-1.8200; 1.7240], I2 = 98.6%). Postoperative pain on day 1 (SMD -0.0885, 95%CI [-0.4368; 0.2598], I2 = 98.9%), day 3 (SMD -0.2118, 95%CI [-0.6110; 0.1873], I2 = 99.5%), and later than day 7 (SMD 0.0924, 95%CI [-0.2491; 0.4338], I2 = 98.6%) in the treatment group was not significantly reduced relative to the control group. When compared to the control group, BiZact™ did not reduce the incidence of secondary postoperative bleeding control in the operation room (OR 0.5711, 95%CI [0.2476; 1.3173], I2 = 32.1%), primary bleeding (OR 0.4514, 95%CI [0.0568; 3.5894], I2 = 0.0%), or all postoperative bleeding events (OR 0.8117, 95%CI [0.5796; 1.1368], I2 = 26.3%). Conclusions: This study demonstrated that using the BiZact™ device for tonsillectomy significantly decreased the operative time but could not effectively reduce intraoperative bleeding or postoperative pain and bleeding.

Secondary Hemophagocytic Lymphohistiocytosis Following Dostarlimab Treatment in a Patient With Metastatic Endometrial Cancer.

Immunotherapy is a rapidly expanding cancer treatment strategy. Dostarlimab is administered as the first-line treatment for metastatic endometrial cancer in combination with chemotherapy. Herein, we describe the case of a 72-year-old female patient who developed hemophagocytic lymphohistiocytosis after receiving a single dose of 500 mg of dostarlimab. The patient's clinical outcome improved after treatment with ruxolitinib and corticosteroids. Oncological treatment was resumed in combination with chemotherapy alone.

Low-Dose Oral Minoxidil and Associated Adverse Events: Analyses of the FDA Adverse Event Reporting System (FAERS) With a Focus on Pericardial Effusions.

BACKGROUND: Low-dose oral minoxidil (LDOM) is used to treat hair loss, but the literature on its safety profile is relatively sparse. AIMS: Using the FDA Adverse Event Reporting System (FAERS) database, we determined signals for adverse events (AEs) with LDOM use. METHODS: Four sets of case/noncase study disproportionality analyses were conducted to determine reporting odds ratio (ROR) for 10 AEs including pericardial effusion (PE). The oral minoxidil dose ranges were: (i) ≤1.25 mg (i.e., 0-1.25 mg), (ii) ≤2.5 mg (i.e., 0-2.5 mg), (iii) ≤5 mg (i.e., 0-5 mg), and (iv) ≤10 mg (i.e., 0-10 mg). RESULTS: For ≤1.25 mg, we detected a signal for PE (ROR = 16.41, 95% CI: 2.29, 117.37, p < 0.05). For ≤2.5 mg, the analyses detected a signal for PE (ROR = 13.30, 95% CI: 5.96, 29.68, p < 0.05); the ROR in the absence of cardiac impairment was 5.34 (95% CI: 1.33, 21.37, p < 0.05); in the presence of cardiac impairment, the ROR was 49.42 (95% CI: 18.27, 133.66, p < 0.05). A signal for PE was also detected at ≤5 and ≤10 mg. For PE, there was a significant (p < 0.05) association with a patient outcome of "life threatening" only at the ≤10 mg dose range. CONCLUSIONS: Our study, the first FAERS-based signal detection study for LDOM, found significant associations between LDOM use and several AEs. In the absence of causal evidence, these correlations warrant more attention regarding safe use of LDOM. Until more safety data are available, we recommend using LDOM at the lowest effective dose (≤5 mg/day).

Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

OBJECTIVES: Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. METHODS: In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed. RESULTS: In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. CONCLUSIONS: The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Uptake, adverse effect, and associated factors of COVID-19 vaccine among those living with human immunodeficiency virus, at Bole sub-city health facility Addis Ababa, Ethiopia.

COVID-19 vaccination in African people living with human immunodeficiency virus remains understudied, with limited research in Ethiopia that fails to consider contextual differences. To assess uptake, adverse effects, and associated factors of COVID-19 vaccine among PLWHA in Addis Ababa, Ethiopia, 2022. An institutional cross-sectional study design was employed among 404 participants. Sample selected by systematic random sampling technique. Descriptive and inferential statistical analyses were carried out. Finally, results were presented using Crude Odd Ratio, Adjusted Odd Ratio, and 95% Confidence Interval. Result: Out of all participants, 79% (314) received at least one dose of any type of COVID-19 vaccine, with varying percentages taking one (29.3%), two (50.3%), and three (20.4%) doses of the vaccine. Being knowledgeable (moderate and good) (AOR = 0.06, 95% CI: 0.01, 0.5) and medium attitude (AOR = 1.1, 95% CI: 0.7, 1.3) had a statistically significant association with the uptake of the COVID-19 vaccine. The prevalence of adverse events was 27.8% (110). More than three-quarters of participants were vaccinated for the COVID-19 vaccine. Moderate knowledge and medium attitude have a significant association with the uptake of the COVID-19 vaccine. Nearly a quarter of participants experienced adverse events related to COVID-19. Continued efforts are essential to overcome barriers to achieving full vaccination coverage for the most vulnerable in low-income countries. Addressing hesitancy, monitoring side effects, and implementing effective communication and strategies are crucial for widespread COVID-19 vaccination and public health safety in these regions.

The annoyance of singultus: a case report of a rare adverse effect after epidural steroid injection.

OBJECTIVE: Cervical epidural steroid injections (ESIs) can provide effective pain management for patients suffering from chronic neck pain due to various pathological changes of the cervical spine. There are several rare adverse effects reported from interventional pain procedures, including persistent hiccups ("singultus"). Based on a limited number of cases, we propose a modified treatment algorithm for this adverse outcome (Fig. 3). CASE REPORT: Singultus has been documented as an adverse effect of interventional pain procedures, including epidural steroid, facet joint, and sacroiliac joint injections. We describe the case of a general contractor who presented to our clinic with chronic neck pain and central canal stenosis. The patient received an uncomplicated lumbar ESI in the past and was recommended for a cervical interlaminar ESI. After an uneventful C6-C7 interlaminar ESI with dexamethasone, 1% lidocaine, and normal saline the patient developed singultus. Baclofen was sent to his pharmacy, but this was unsuccessful at alleviating his hiccups. The patient was subsequently started on chlorpromazine and found relief from his symptomatology. CONCLUSION: Persistent hiccups after ESI or interventional pain procedures can be treated with conservative measures and non-pharmacologic methods, with escalation to therapy with baclofen, gabapentin, pregabalin, metoclopramide, chlorpromazine, other antipsychotic or antidopaminergic agents, and possible dual or triple therapy if further indicated.

Periocular granulomatous inflammatory lesions mimicking conjunctival melanoma recurrence in the setting of systemic nivolumab treatment.

Purpose: Conjunctival melanoma is a rare neoplasm with high rates of recurrence and metastasis. Traditional management includes surgical excision and cryotherapy, followed by adjuvant therapy as needed. Immune checkpoint inhibitors, including nivolumab, are a targeted treatment option with improved survival rates. However, various immune-related adverse effects have been reported with these drugs. While systemic granulomatous inflammation is a documented systemic side effect, it has rarely been reported in the conjunctiva and ocular adnexa. Observation: A patient with a history of recurrent metastatic conjunctival melanoma presented with both a left sub-conjunctival and upper eyelid lesion after the commencement of treatment with nivolumab. The lesions were excised with a clinical suspicion for metastasis and consisted of noncaseating granulomatous inflammation with no evidence of malignancy on histopathologic examination. Infectious and primary autoimmune etiologies were ruled out. Conclusion and importance: This is a biopsy-proven case of periocular immune checkpoint inhibitor-associated granulomatous inflammation.

Reversible Second-Degree Heart Block Attributed to Ondansetron: A Rare Side Effect.

A primigravida at 36 weeks with gestational diabetes mellitus and hypothyroidism and no prior chronic medical illness was admitted for safe confinement. A cesarean section was required to deliver the baby with breech presentation complicated by a slow progression of labor. Asymptomatic sinus bradycardia with a heart rate of 40 per minute was observed during the induction of anesthesia. Before bupivacaine administration for spinal anesthesia, she was administered pantoprazole 40 mg and ondansetron 4 mg intravenously. ECG recording showed a type 1 Mobitz second-degree heart block. Follow-up ECG showed progression of heart block to type 2 Mobitz second-degree heart block. The second-degree heart block persisted for 16 hours, during which the patient was asymptomatic, and the ventricular rate was maintained at a range of 60-80 per minute. After normalization of rhythm, the patient was observed in the ICU. She received another dose of ondansetron 4 mg intravenously for vomiting, and the heart block recurred. The rhythm disturbance was attributed to ondansetron. Her rhythm normalized after 36 hours, and she was subsequently discharged home three days later.

Mutations Associated With High-Grade irAEs in NSCLC Patients Receiving Immunotherapies.

OBJECTIVES: Compared to low-grade irAEs, high-grade irAEs are more often dose-limiting and can alter the long-term treatment options for a patient. Predicting the incidence of high-grade irAEs would help with treatment selection and therapeutic drug monitoring. MATERIALS AND METHODS: We performed a retrospective study of 430 stage III and IV patients with non-small cell lung cancer (NSCLC) who received an immune checkpoint inhibitor (ICI), either with or without chemotherapy, at a single comprehensive cancer center from 2015 to 2022. The study team retrieved sequencing data and complete clinical information, including detailed irAEs medical records. Fisher's exact test was used to determine the association between mutations and the presence or absence of high-grade irAEs. Patients were analyzed separately based on tumor subtypes and sequencing platforms. RESULTS: High-grade and low-grade irAEs occurred in 15.2% and 46.2% of patients, respectively. Respiratory and gastrointestinal irAEs were the 2 most common irAEs. The distribution of patients with or without irAEs was similar between ICI and ICI+chemotherapy-treated patients. By analyzing the mutation data, we identified 5 genes (MYC, TEK, FANCA, FAM123B, and MET) with mutations that were correlated with an increased risk of high-grade irAEs. For the adenocarcinoma subtype, mutations in TEK, MYC, FGF19, RET, and MET were associated with high-grade irAEs; while for the squamous subtype, ERBB2 mutations were associated with high-grade irAEs. CONCLUSION: This study is the first to demonstrate that specific tumor mutations correlate with the incidence of high-grade irAEs in patients with NSCLC treated with an ICI, providing molecular guidance for treatment selection and drug monitoring.