Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

儿童外科教学方法实践及探讨

目的探讨儿童外科的教学特点及教学方法,提高儿外科医生的总体执业水平,促进儿童外科学的发展。方法通过分析四川大学华西医院多年儿童外科疾病的临床教学实践经验,总结出适合医学生、初级儿童外科专科医生的实用的教学方法及经验。结果结合儿童外科特有的疾病特点所总结出的故事式讲述教学、典型病例教学、漫画形式学习、比较学习法及多媒体素材教学五种方式是非常适合儿童外科教学的方法。能够加深记忆,提高兴趣,轻松快捷,事半功倍的掌握相关医学专业知识。结论独特有趣的儿童外科教学方法可提高医学生及儿童外科初级从业者的学习兴趣、专业知识和执业水平。     

Cervicofacial non-tuberculous mycobacterial lymphadenitis: clinical determinants of incomplete surgical removal

In patients with non-tuberculous mycobacterial cervicofacial lymphadenitis, incomplete surgical removal of infected lymph nodes leads to delayed healing and a higher recurrence rate, with eventual spontaneous drainage through the skin. However, complete surgical removal is not always achievable due to the extent of the infected tissue and proximity to vulnerable structures, such as the facial or accessory nerve. The aim of this study was to identify the clinical determinants of the (in)ability to perform complete surgical removal. The electronic health records of patients aged 0–15 years with bacteriologically proven non-tuberculous mycobacterial cervicofacial lymphadenitis, who underwent surgical treatment and preoperative sonographic imaging, were analysed. This was a case–control study. A total of 103 patients met the inclusion criteria. Most of the infections were unilateral, submandibular, and caused by Mycobacterium avium. Multiple logistic regression analysis revealed that higher age (odds ratio 1.24, 95% confidence interval 1.04–1.47) and fistulization (odds ratio 3.15, 95% confidence interval 1.13–8.75) were significantly associated with a limited ability to surgically remove all infected tissue. However, a larger sonographic lymph node size was not significantly associated. These findings could aid clinicians when informing the parent(s)/guardian(s) of the patient preoperatively and in properly estimating the intraoperative and postoperative course.     

The marks of gunshot wounds to the face

IntroductionThis article deals with the occurrence of health problems due to gunshot wounds to the face among military police officers, in the metropolitan region of Rio de Janeiro, who were submitted to surgery at the Oral and Maxillofacial Surgery and Traumatology Clinic of Hospital Central da Polícia Militar.ObjectiveTo identify the profile of patients submitted to surgery as a result of gunshot wounds, the anatomical distribution of maxillofacial fractures, the identified sequelae and complications, the health specialties involved in the rehabilitation of these patients, and to discuss the social, emotional and work performance-related effects of work among these subjects.MethodsA retrospective epidemiological study was carried out based on secondary data from military police officers who were submitted to surgery at Hospital Central da Polícia Militar due to gunshot wounds from June 2003 to December 2017.ResultsDuring the study period, 778 surgeries were performed in the operating room by the Oral and Maxillofacial Surgery and Traumatology service at Hospital Central da Polícia Militar, 186 of which were due to gunshot wounds (23.9%). All patients were males and the mean age 34.7 years. Bone segment loss was the most common sequela. Facial esthetic impairment and reports of insomnia were the most often identified late consequences of impact on health and social life. Regarding the occupational impacts of the sustained injury, the mean time away from work due to medical leave for the treatment of maxillofacial injuries was 11.7 months.ConclusionThe treatment of gunshot wounds patients with facial injuries requires multiple surgical interventions and their rehabilitation requires the involvement of different health specialties. Further studies are needed to qualitatively analyze the impact of this type of facial trauma on the patients' lives and their social consequences.     

Pulmonary Carcinosarcoma: A Surveillance,Epidemiology, and End Results (SEER) Analysis

IntroductionPulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for < 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage.Patients and MethodsSEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods.ResultsA total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P < .001; DSS: 54 vs. 8 months, P < .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P < .001) and DSS (32 months; P < .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months).ConclusionTreatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans.