不同类型鼻中隔偏曲53例矫正方法选择

目的探讨针对不同的鼻中隔偏曲类型,使用不同手术方式矫正鼻中隔偏曲的临床效果。方法对10例整体偏曲、24例局限性单部位偏曲、19例多部位局限性偏曲患者,分别使用传统鼻中隔黏膜下切口、单个“L”形切口、多个“L”形切口等方法矫正鼻中隔,并对其临床疗效进行评价。结果术后第1周复查中,2例鼻中隔整体偏曲、2例多部位局限性偏曲的切口侧渗出物较多。3个月复查见所有病例矫正后的鼻中隔偏曲形态良好,无鼻中隔穿孔以及鼻中隔摆动;除5例仍有轻微的交替性鼻塞外,其余患者术后鼻腔通气改善,头痛症状消失,患者感觉满意。结论根据鼻中隔偏曲的部位和类型,选择不同的手术方法进行鼻中隔矫正,临床效果好,组织损伤少,减少并发症和患者的痛苦。     

The saccharin method for testing mucociliary function in patients suspected of having primary ciliary dyskinesia

In order to evaluate the clinical value of the saccharin test as a practical and simple measure of mucociliary clearance, nasal mucociliary clearance (NMCC) and ciliary ultrastructure were studied in 22 patients suspected of having primary ciliary dyskinesia (PCD) based on the saccharin test. Ten patients fulfilling the diagnostic criteria of PCD had a pathological response to the saccharin test (transport time greater than 60 minutes), and this was consistently associated with ultrastructural defects, specific for PCD. These results validate the suitability of the clinical use of the saccharin test as a screening procedure for NMCC. The false-negative results obtained in three cases of PCD, all with borderline values, cannot be ascribed to ineffectiveness of the test, but rather to the persistence of some motility by certain defective cilia, detectable by microphoto-oscillographic investigation of specimens obtained by nasal biopsy or brushing.     

Anti‐inflammatories and mucociliary clearance therapies in the age of CFTR modulators

Cystic fibrosis (CF) is a genetic and life‐limiting disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. This multi‐system disease is characterized by progressive lung disease and pancreatic insufficiency amongst other manifestations. CFTR primarily functions as a chloride channel that transports ions across the apical membrane of epithelial cells but has other functions, including bicarbonate secretion and inhibition of sodium transport. Defective CFTR disrupts these functions, causing viscous and dehydrated mucus to accumulate, compromising the airway lumen and contributing to obstructive pulmonary disease. The combination of CFTR dysfunction, mucus obstruction, and infection drive an exaggerated and dysfunctional inflammatory response, which contributes to irreversible airway destruction and fibrosis. CFTR modulators, an exciting new class of drugs, increase the expression and/or function of CFTR variant protein and improve multiple clinical endpoints, such as lung function, pulmonary exacerbation rates, and nutritional status. However, these genotype‐specific drugs are not universally available, the clinical response is variable, and lung function still declines over time when bronchiectasis is established. Consequently, even in the age of CFTR modulators, we must target other important aspects of the CF airway disease, such as inflammation and mucociliary clearance. This review highlights the mechanisms of inflammation and mucus accumulation in the CF lung and discusses anti‐inflammatory and mucociliary clearance agents that are currently in development focusing on compounds for which clinical trial data have recently become available.     

A case of relapsing polychondritis with bilateral sensorineural hearing loss and perforation of the nasal septum at the onset

A 33-year-old woman suffered from epistaxis and perforation of the nasal septum. Based on a biopsy of nasal mucosa, Wegener's granulomatosis was suspected initially. Her nasal symptoms improved spontaneously, but tinnitus, hearing loss, and dizziness appeared within 3 months. Laboratory analyses revealed no inflammation, and antineutrophil cytoplasmic antibodies were negative. Audiometry revealed bilateral sensorineural hearing loss. A second biopsy of the nasal septum showed an inflammatory change in the cartilage. Thus we diagnosed early-stage relapsing polychondritis.     

von Willebrand factor contributes to longer half‐life of PEGylated factor VIII in vivo

PEGylation of B‐domain deleted factor VIII (PEG‐FVIII‐BDD) prolongs the half‐life of the molecule by approximately twofold in animals (Mei et al., Blood 2010; 116 : 270). To investigate the role of von Willebrand factor (vWF) in the catabolism of PEG‐FVIII‐BDD in vivo, a FVIII‐BDD mutant (F8V), which is incapable of binding vWF, was generated by deleting the vWF‐binding region in the a3 domain of FVIIII‐BDD. F8V was expressed, purified and PEGylated by site‐specific conjugation. The biochemical and biological properties of F8V and PEGylated F8V (PEG‐F8V) were evaluated in vitro and in vivo. The specific activity of purified F8V by a chromogenic assay was similar to FVIII‐BDD and PEGylation had minimal impact on the specific activity of F8V in this assay. Analysis by Biacore indicated that both F8V and PEG‐F8V display greatly reduced vWF binding in vitro. Pharmacokinetic studies in FVIII knockout (HaemA) mice showed that the terminal half‐life (T_1/2) of F8V was dramatically reduced relative to FVIII‐BDD (0.6 h vs. 6.03 h). PEGylation of F8V promoted a significant increase in T_1/2, although PEGylation did not fully compensate for the loss in vWF binding. PEG‐F8V showed a shorter T_1/2 than PEG‐FVIII‐BDD both in HaemA mice (7.7 h vs. 14.3 h) and in Sprague‐Dawley male rats (2.0 ± 0.3 h vs. 6.0 ± 0.5 h). These data demonstrated that vWF contributes to the longer T_1/2 of PEG‐FVIII‐BDD. Furthermore, this suggests that the clearance of the FVIII:vWF complex, through vWF receptors, is not the sole factor which places an upper limit on the duration of PEG‐FVIII circulation in plasma.     

Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real‐world setting

In the present multicentre, open‐label, prospective, phase III study, we evaluated the real‐world effectiveness and ease of use of nasal glucagon (NG) in the treatment of moderate/severe hypoglycaemic events (HEs) in adults with type 1 diabetes (T1D). Patients and caregivers were taught how to use NG (3 mg) to treat moderate/severe HEs, record the time taken to awaken or return to normal status, and measure blood glucose (BG) levels over time. Questionnaires were used to collect information about adverse events and ease of use of NG. In the efficacy analysis population, 69 patients experienced 157 HEs. In 95.7% patients, HEs resolved within 30 minutes of NG administration. In all the 12 severe HEs, patients awakened or returned to normal status within 15 minutes of NG administration without additional external medical help. Most caregivers reported that NG was easy to use. Most adverse events were local and of low to moderate severity. In this study, a single, 3‐mg dose of NG demonstrated real‐life effectiveness in treating moderate and severe HEs in adults with T1D. NG was well tolerated and easy to use.     

Evaluation of yield of currently available diagnostics by sample type to optimize detection of respiratory pathogens in patients with a community‐acquired pneumonia

Background

For the detection of respiratory pathogens, the sampling strategy may influence the diagnostic yield. Ideally, samples from the lower respiratory tract are collected, but they are difficult to obtain.

Objectives

In this study, we compared the diagnostic yield in sputum and oropharyngeal samples (OPS) for the detection of respiratory pathogens in patients with community-acquired pneumonia (CAP), with the objective to optimize our diagnostic testing algorithm.

Methods

Matched sputum samples, OPS, blood cultures, serum, and urine samples were taken from patients (>18 years) with CAP and tested for the presence of possible respiratory pathogens using bacterial cultures, PCR for 17 viruses and five bacteria and urinary antigen testing.

Results

When using only conventional methods, that is, blood cultures, sputum culture, urinary antigen tests, a pathogen was detected in 49·6% of patients (n = 57). Adding molecular detection assays increased the yield to 80%. A pathogen was detected in 77 of the 115 patients in OPS or sputum samples by PCR. The sensitivity of the OPS was lower than that of the sputum samples (57% versus 74%). In particular, bacterial pathogens were more often detected in sputum samples. The sensitivity of OPS for the detection of most viruses was higher than in sputum samples (72% versus 66%), except for human rhinovirus and respiratory syncytial virus.

Conclusion

Addition of PCR on both OPS and sputum samples significantly increased the diagnostic yield. For molecular detection of bacterial pathogens, a sputum sample is imperative, but for detection of most viral pathogens, an OPS is sufficient.     

Simple cystatin C formula compared to sophisticated CKD-EPI formulas for estimation of glomerular filtration rate in the elderly

Despite the fact that the serum creatinine level is notoriously unreliable for the estimation of glomerular filtration rate (GFR) in the elderly, the serum creatinine concentration and serum creatinine-based formulas, such as the Modification of Diet in Renal Disease study equation (MDRD) are the most commonly used markers to estimate GFR. Recently, serum cystatin C-based formulas, the newer creatinine formula (the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI creatinine formula), and an equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) were proposed as new GFR markers. The aim of our study was to compare the MDRD formula, CKD-EPI creatinine formula, CKD-EPI creatinine and cystatin formula, and simple cystatin C formula (100/serum cystatin C) against (51) Cr-EDTA clearance in the elderly. A total of 317 adult Caucasian patients aged >65 years were enrolled. In each patient, (51) Cr-EDTA clearance, serum creatinine, and serum cystatin C were determined, and the GFR was calculated using the MDRD formula, CKD-EPI formulas, and simple cystatin C formula. Statistically significant correlations between (51) Cr-EDTA clearance and all formulas were found. In the receiver operating characteristic (ROC) curve analysis with a cut-off of GFR 45 mL/min/1.73 m(2), a higher diagnostic accuracy was achieved with the equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) than the MDRD formula (P < 0.013) or CKD-EPI creatinine formula (P < 0.01), but it was not higher than that achieved for the simple cystatin C formula (P = 0.335). Bland and Altman analysis for the same cut-off value showed that the creatinine formulas underestimated and the simple cystatin C formula overestimated measured GFR. All equations lacked precision. The accuracy within 30% of estimated (51) Cr-EDTA clearance values differ according to the stage of CKD. Analysis of the ability to correctly predict GFR below and above 45 mL/min/1.73 m(2) showed a high prediction for all formulas. Our results indicate that the simple cystatin C formula, which requires just one variable (serum cystatin C concentration), is a reliable marker of GFR in the elderly and comparable to the creatinine formulas, including the CKD-EPI formulas.