Highseverinsen9048

Statins are the most widely used cholesterol-lowering drugs for cardiovascular diseases prevention. However, some patients are refractory to treatment, whereas others experience statin-related adverse events (SRAE). It has been increasingly important to identify pharmacogenetic biomarkers for predicting statin response and adverse events. This case report describes a female patient with familial hypercholesterolemia (FH) who showed late response to rosuvastatin and experienced myalgia on statin treatment. In the first visit (V1), the patient reported myalgia to rosuvastatin 40 mg, which was interrupted for a 6-week wash-out period. In V2, rosuvastatin 20 mg was reintroduced, but her lipid profile did not show any changes after 6 weeks (V3) (LDL-c 402 vs. 407 mg/dL). Her lipid profile markedly improved after 12 weeks of treatment (V4) (LDL-c 208 mg/dL), suggesting a late rosuvastatin response. Her adherence to treatment was similar in V1 and V3 and no drug interactions were detected. Pharmacogenetic analysis revealed that the patient carries low-activity variants in SLCO1B1*1B and*5, SLCO1B3 (rs4149117 and rs7311358), and ABCB11 rs2287622, and the non-functional variant in CYP3A5*3. The combined effect of variants in pharmacokinetics-related genes may have contributed to the late response to rosuvastatin and statin-related myalgia. Therefore, they should be considered when assessing a patient's response to statin treatment. selleck inhibitor To the best of our knowledge, this is the first report of a pharmacogenetic analysis on a case of late rosuvastatin response.Diffuse idiopathic skeletal hyperostosis (DISH), asymptomatic in most cases, is a degenerative condition that commonly leads to anterior cervical osteophytes in most elderly patients. Clinically significant airway compression is rare. However, in some cases, the seemingly insignificant osteophytes could become a threat to airway management during intubation. Here we present a case of an 82-year-old man diagnosed as DISH and scheduled for cervical surgery. Radiographic imaging did not indicate the airway compromise. Preoperative airway assessment indicated modified Mallampati scoring of class III. However, an unexpected large bulge protruding from posterior pharyngeal wall blocked video laryngoscopy assisted intubation. Intubation with direct laryngoscope, laryngeal mask airway (LMAD) and Shikani optical stylet were failed. Only flexible fiberoptic nasal intubation was performed successfully. After surgery, an anatomically matched and patient-specific 3D printed model was made to help more direct and comprehensive estimation of the size and the location of the osteophyte. The relationship of the airway compromise and osteophytes was revealed in DISH patients for the first time with the aid of 3D printed model. The eccentric growth of the cervical osteophytes occupied large portion of the laryngopharynx space and prohibited the direct placement of the tracheal tube. This case is a rare presentation of the management of a DISH patient with unexpected difficult airway. We propose for the first time that different intubation strategies should be considered for potential difficulty airway in DISH patients according to the size and location of the osteophytes. For potential difficult airway management of DISH patients, 3D printing technique is a promising way of preoperative airway assessment.This study aimed to analyze the diagnosis and treatment of one case of pulmonary angiosarcoma (PPA) retrospectively. The main manifestation of this female patient was cough, hemoptysis and dyspnea. Computed tomography (CT) of the chest revealed multiple small nodules and ground-glass patches in both lungs suggesting of diffuse alveolar hemorrhage (DAH). Laboratory examination revealed decreased hemoglobin and platelet counting, normal coagulation function. Results of rheumatic markers testing including antinuclear antibody (ANA), anti-extractable nuclear antigen antibody (ENA), vasculitis marker, and antiphospholipid antibody were negative. Tumor markers were negative. Sputum smear, sputum culture, and alveolar lavage fluid culture showed negative results. The bone marrow smear was essentially normal. The patient received methylprednisolone pulse therapy (250 mg daily × 5 days) and immunoglobin (20 d daily × 7 days) treatment, but her hemoptysis persisted. Bilateral pleural effusion drainage found a large amount of bloody effusion, but cytology of the pleural fluid showed negative results. The clinical symptoms, laboratory results, imaging findings, and pathological features of the patient were summarized, and problems in diagnosis and treatment were discussed. A thoracoscopic lung biopsy was performed and the diagnosis of PPA was confirmed by pathology and immunohistochemistry (IHC) staining. This case suggested that the possibility of PPA should be considered in patients with DAH, but with negative findings in routine examinations, lung biopsy is usually required.

Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients.

A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future.

This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

NCT04280822 (https//www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019.

NCT04280822 (https//www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019.