Tezepelumab improved chronic rhinosinusitis with nasal polyps in a Patient with aspirin exacerbated respiratory disease.

Introduction: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) have more severe sinus disease than those without AERD. CRSwNP associated with type 2 inflammation and AERD can be difficult to control with standard medical therapy and sinus surgery. Case study: 74-year-old Japanese woman with chronic sinusitis since age 50 and asthma since age 60. At age 64, she began to experience asthma exacerbations and was started on short-term corticosteroid therapy with prednisolone. At age 70, she experienced urticaria, nasal congestion, and wheezing after taking an NSAID; based on an NSAID provocation test, we diagnosed the patient with AERD and CRSwNP. A diagnosis of severe eosinophilic chronic rhinosinusitis was also made based on the scoring system and algorithm used in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis. Results: Treatment with benralizumab (30 mg), formoterol-fluticasone combination via pressurized metered inhaler (1000 µg), and leukotriene receptor antagonist improved the asthma symptoms and exacerbations so the short-term prednisolone was stopped; however, nasal congestion and olfactory dysfunction (hyposmia) persisted, and peripheral blood eosinophil count (peak, 1500 cells/µL) and fractional exhaled nitric oxide (peak, 42 ppb) became elevated. Swapping the benralizumab for monthly tezepelumab (210 mg) improved not only the asthma symptoms but also the nasal congestion, olfactory dysfunction, eosinophil count (<300 cells/µL), and fractional exhaled nitric oxide level [8ppb]. Conclusion: Changing from benralizumab to tezepelumab improved asthma symptoms, nasal obstruction, and olfactory dysfunction in elderly, female, Japanese patient with AERD and CRSwNP.

A Case of Type I Food Allergy Induced by Monosodium Glutamate.

Monosodium glutamate (MSG), a salt form of a non-essential amino acid, is widely used as a food additive, particularly in Asian cuisines, due to its unique flavor-enhancing qualities. Type I allergic reactions to MSG have not previously been reported. Our patient, a 21-year-old woman, was 14 years old when she first noticed swelling of her tongue (but no oral itching, diarrhea, or abdominal pain) after eating various snack foods. Current skin prick testing elicited a weak positive reaction to MSG. We then performed an oral challenge test during which our patient ingested potato snacks. Subsequent histology showed telangiectasia of the buccal mucosa, interstitial edema in the subepithelial submucosa, and mast cell infiltration. Oral mucosal challenge tests using sodium glutamate confirmed oral swelling in this patient. This report is the first to confirm a case of type 1 allergy to MSG by combining pathology findings with the results of challenge testing.

Intravenous cyclophosphamide and immunoglobulin ameliorated visual field defects in a patient with eosinophilic granulomatosis with polyangiitis.

Treating ocular involvement in eosinophilic granulomatosis with polyangiitis (EGPA) can be challenging. We present the case of a 37-year-old woman with EGPA who had severe bilateral visual field defects. Laboratory results showed leukocytosis (17,500 WBC/µL, 25.8 % eosinophils), negative MPO-ANCA titer, and elevated PR3-ANCA level (33.2 IU/mL). Diffusion-weighted MRI revealed bilateral hyperintense occipital lesions, which were more prominent on the left. Her therapy initially included a steroid pulse, followed by daily prednisolone, but her visual field defects remained refractory. The addition of intravenous cyclophosphamide (5 courses) and intravenous immunoglobulin decreased her optic neuropathy and resolved her visual field defects.

Limited efficacy of low-dose dexamethasone for the treatment of severe COVID-19 pneumonia: A retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Its symptoms range from mild to severe, with the latter often being life-threatening. This study aims to assess the effects of low-dose dexamethasone (DEX) in mild-to-severe COVID-19 pneumonia and examine the final clinical outcomes to identify the optimal therapeutic dose. METHODS: Clinical data from 132 patients hospitalized for COVID-19 pneumonia between January and October 2021 at Yamato Municipal Hospital were retrospectively analyzed. Based on the ratio of peripheral arterial oxygen saturation (SpO2) to inspired fraction of oxygen (FiO2), patients were categorized into the mild (>450, n = 65), moderate (315-450, n = 55), and severe (<315, n = 12) pneumonia groups. The event of interest was defined as the worsening of the patient's condition during treatment (need to increase FiO2 > 0.1). Patients were treated with low-dose DEX (6.6 mg/day) for 10 days. RESULTS: The event-free survival rate decreased significantly in patients with severe pneumonia compared with in those with mild and moderate pneumonia (Bonferroni-adjusted p < 0.02). A total of 16 patients were treated with high-dose corticosteroids because of severe hypoxia. Recovery was observed in all discharged patients with respiratory condition improvement. Low SpO2/FiO2 at admission was significantly associated with serum C-reactive protein levels. CONCLUSIONS: For Japanese patients with COVID-19, severe pneumonia, and SpO2/FiO2 of <315, it may be necessary to administer a dose of corticosteroids of >6.6 mg DEX.

Eosinophilic granulomatosis with polyangiitis and severe cardiac involvement in a patient surviving for 34 years.

INTRODUCTION: Many studies have reported a poor prognosis for eosinophilic granulomatosis with polyangiitis (EGPA) patients with cardiac involvement. CASE STUDY: A woman developed EGPA at 37 years of age, with weight loss, numbness in the right upper and lower extremities, muscle weakness, skin rash, abdominal pain, chest pain, an increased peripheral blood eosinophil count (4165/µL), and necrotizing vasculitis on peroneal nerve biopsy. The patient was treated with prednisolone, immunosuppressants, intravenous immune globulin, and mepolizumab, but she experienced many relapses, with chest pain, abdominal pain, numbness, and paralysis, over a long period. The patient died from aspiration pneumonia at 71 years of age after undergoing left total hip arthroplasty for left hip neck fracture. RESULTS: Autopsy showed bronchopneumonia in the lower lung lobes on both sides, as well as infiltration of inflammatory cells, including neutrophils and lymphocytes. There was no evidence of active vasculitis in either the lung or colon. At autopsy the heart showed predominantly subendocardial fibrosis and fatty infiltration, but no active vasculitis or eosinophilic infiltration. CONCLUSION: To our knowledge, there have been no autopsy reports of EGPA patients who have survived for 34 years with recurrent cardiac lesions. In this case, the cardiac involvement (active vasculitis and eosinophilic infiltration) had improved by the time of death.

ALK-Rearranged NSCLC With Concomitant HER2-Mutant Breast Cancer Patient Treated With Alectinib, Trastuzumab, and Pertuzumab: A Case Report.

Multiple cancers are a common occurrence, and the choice of treatment can be a challenging decision. The current case report describes a 71-year-old woman with overlapping anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma and HER2-mutant breast cancer, who achieved improvement with concurrent use of the molecularly targeted agents Alectinib, Trastuzumab, and Pertuzumab. A 71-year-old woman was diagnosed with lung adenocarcinoma and brain metastases, and invasive ductal carcinoma of the right breast, HER2-mutant type. In March 2021, a biopsy confirmed the presence of the ALK fusion gene in lung cancer. In April 2021, he started Alectinib and showed shrinkage of lung cancer; in December 2021, a metastatic liver tumor was found, and a liver biopsy diagnosed liver metastasis of breast cancer. Therefore, Alectinib was discontinued in February 2022, and Trastuzumab, Pertuzumab, and Docetaxel were started as chemotherapy for breast cancer. She continued treatment with Trastuzumab and Pertuzumab, but in July 2022, she developed an increase in lung cancer. Her metastatic liver tumor continued shrinking, and she was started on Trastuzumab, Pertuzumab, and Alectinib. After six months of treatment, the patient showed a sustained reduction in both lung cancer, breast cancer, and brain metastases with no adverse events. ALK rearrangement lung cancer often develops in young women, and similarly, breast cancer often develops in women. Therefore, those cancers may occur simultaneously. In such cases, the choice of treatment can be difficult, as both cancers require different approaches. Alectinib has been shown to have a high response rate and prolonged progression-free survival in ALK-rearranged non-small cell lung cancer (NSCLC). Trastuzumab and Pertuzumab are commonly used for the treatment of HER2-mutant breast cancer and have been shown to significantly improve progression-free survival and overall survival. This case report provides evidence that the concurrent use of Alectinib, Trastuzumab, and Pertuzumab can be an effective treatment for patients with overlapping ALK-rearranged NSCLC and HER2-mutant breast cancer. It is important to consider concurrent treatment in patients with multiple cancers to optimize treatment outcomes and improve quality of life. However, further studies are needed to establish the safety and efficacy of this combination of drugs for the treatment of overlapping cancers.

Entrectinib-Induced Heart Failure in a Patient With Metastatic Lung Adenocarcinoma: A Case Report.

Entrectinib is a recently approved multikinase inhibitor to treat advanced c-ros oncogene1 (ROS1) positive non-small cell lung cancer (NSCLC). Although molecular targeted therapy is generally well tolerated, cardiovascular adverse events have been described in recent years. We report a case of NSCLC with ROS1 rearrangement where the patient developed drug-induced heart failure after receiving entrectinib. A 74-year-old non-smoker female patient was diagnosed with stage IVB lung adenocarcinoma with ROS-1 positive and right breast cancer stage I. We started on entrectinib as the first-line therapy for lung cancer. Five days after, she developed oral dysesthesia and blood creatinine increased. These findings gradually worsened, so we temporarily discontinued entrectinib. After withholding the drug for 14 days, these findings improved, and we resumed entrectinib at a reduced dose. On day 19 of the reduced entrectinib dose, she presented to the outpatient with shortness of breath and bilateral lower extremity edema, accompanied by respiratory failure. Laboratory evaluation revealed elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), troponin I, creatine kinase (CK), and C reactive protein (CRP), and transthoracic echocardiogram showed congestive heart failure (CHF) with a preserved ejection fraction (HFpEF). She did not complain of chest pain and fever, so we did not consider ischemic heart disease and viral myocarditis in the initial evaluation. There was no other causative cause of CHF. Therefore, we suspected entrectinib-related heart failure. Her symptoms improved and she recovered her cardiac function to baseline within a week of discontinuation of entrectinib and standard heart failure treatment. She developed heart failure after a one-step dose reduction and was prone to cardiotoxicity due to entrectinib. Considering that she could be treated with crizotinib, we decided discontinuation of entrectinib permanently. This case report highlights the potential cardiotoxicity of entrectinib and suggests the need for close monitoring of the cardiac functions of patients receiving entrectinib.

Effects of anesthetic agents on in vivo axonal HCN current in normal mice.

OBJECTIVE: The objective was to study the in vivo effects of anesthetic agents on peripheral nerve excitability. METHODS: Normal male mice were anesthetized by either isoflurane inhalation or a combination of medetomidine, midazolam, and butorphanol intraperitoneal injection ("triple agents"). Immediately after induction, the tail sensory nerve action potential was recorded and its excitability was monitored. RESULTS: Under both anesthetic protocols, there was an interval excitability change by long hyperpolarizing currents. There was greater threshold reduction approximately 30min post induction, in comparison to immediately post induction. Other excitability parameters were stable over time. Modeling suggested interval suppression of internodal H conductance or leak current. CONCLUSIONS: Anesthetic agents affected responses to long hyperpolarizing currents. SIGNIFICANCE: Axonal excitability during intraoperative monitoring may be affected by anesthetic agents. Interpretation of interval excitability changes under anesthesia requires caution, especially with long hyperpolarizing currents.