Interpretation,pitfalls of biomarkers in diagnosis of invasive fungal diseases

BackgroundInvasive Fungal Diseases (IFD), account for high morbidity and mortality in immunocompromised and seriously ill patients worldwide. Early, faster and accurate diagnosis with timely and appropriate patient management is critical for improved patient outcome and antifungal stewardship. Clinical/radiological presentations in IFD are non-specific and microscopy/culture based tests have low sensitivity and long turnaround time. Biomarkers have clinical utility for diagnosing IFD but their interpretation is not straight forward.ObjectivesThis review discusses the salient characteristics, clinical usefulness and limitations of common biomarkers such as Galactomannan (GM), 1–3, β D glucan (βDG), mannan, anti-mannan antibody (Mn/antiMn), Cryptococcal antigen test (CrAg), Nucleic Acid Amplification (NAA) tests and next generation sequencing for diagnosing IFD.ContentsFungal biomarkers are useful adjuncts as screening and diagnostic tools for IFD and are much more suited for ‘ruling out’ rather than ‘ruling in’ disease. GM, NAA tests are promising biomarkers for screening of invasive Aspergillosis in high risk asymptomatic patients who are not on antifungal therapy and for diagnosis of breakthrough infections in symptomatic patients. 1–3, β D glucan has limitations both as a ‘rule in’ and ‘rule out’ test and is useful in only specific clinical settings. Two consecutive positive 1-3-βDG tests or combined positivity with GM increases its specificity. Mn/antiMn, T2Candida nano diagnostic panel are promising candidates for diagnosing invasive candidiasis. Combining two or more biomarkers improves the sensitivity for prompt initiation of antifungal therapy and the negative predictive value for suspension of empirical treatment.Serum CrAg test is a good ‘rule in’ rather than a ‘rule out’ test in immunocompetent patients but has good diagnostic accuracy in immunocompromised patients. Detection of single nucleotide polymorphisms by next generation sequencing is useful for fungal characterization and identification of host determinants responsible for increased susceptibility to fungal infections but is still in experimental stages.     

改良眶隔法和传统睑板法切开重睑术的术后重睑形态、瘢痕发生率、角膜暴露率比较研究

目的 比较改良眶隔法和传统睑板法切开重睑术中的应用效果及对术后重睑形态、瘢痕发生率、角膜暴露率的影响。方法 选取2020年3月-2021年3月首都医疗爱育华医院收治的80例单睑患者，采用随机数字表法将其分对照组和观察组，各40例。对照组接受传统睑板法切开重睑术，观察组接受改良眶隔法切开重睑术，比较两组术后重睑形态、瘢痕发生率、角膜暴露率、并发症发生率。结果 观察组总有效率高于对照组，差异有统计学意义（P＜0.05）；观察组GAIS评分高于对照组，VAS评分低于对照组，差异有统计学意义（P＜0.05）；观察组右侧角膜暴露率增加值、左侧角膜暴露率增加值高于对照组，差异有统计学意义（P＜0.05）；观察组并发症发生率为5.00%，低于对照组的22.50%，差异有统计学意义（P＜0.05）。结论 相比于传统睑板法切开重睑术，改良眶隔法切开重睑术不会过度增加术后角膜暴露率，术后瘢痕发生率更低，重睑形态更理想，患者接受度更高。     

Emerging issue of fluconazole-resistant candidemia in a tertiary care hospital of southern italy: time for antifungal stewardship program

An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%.This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.     

微创性肺表面活性物质治疗新生儿呼吸窘迫综合征的疗效及肺部影像学表现

目的探讨微创性肺表面活性物质(LISA)治疗新生儿呼吸窘迫综合征(NRDS)的疗效及肺部影像学表现。方法择取郑州市第二人民医院于2018年3月至2021年2月收治的70例NRDS患儿,随机分为两组。对照组实行INSURE治疗方案,观察组采用LISA治疗方案,比较两组临床治疗情况、血气分析指标、不良反应事件及肺部影像学表现。结果两组二次PS使用率、给药成功率、NAPAP时间及住院时间比较,差异无统计学意义(P>0.05);而观察组72h内MV率为8.57%,低于对照组(28.57%,P<0.05);于T₂、T₃、T₄及T₅时点,两组PaO₂水平较T1时点均上升,PaCO₂、FiO₂水平则下降(P<0.05);于T₄、T₅时点,观察组FiO2水平低于对照组(P<0.05);两组不良反应及并发症发生率比较,差异均无统计学意义(P>0.05);经影像学特征分析,两组共计7例重度病症(“雪花征”样肺实变,已累及所有分区)、48例中度病症(“雪花征”样肺实变,尚未累及全部肺野)及15例轻度病症(呈“磨玻璃征”样肺实变,累计范围不限),经PS治疗6h、12h及24h后,给予LUS复查,两组NRDS患儿肺脏影像学评分均低于治疗前(P<0.05)。结论LISA及INSURE治疗NRDS均可起到较好疗效,但LISA整体获益更高,血气指标有一定改善,可降低72h内MV使用率,且不增加不良反应事件风险。     

高龄直肠癌患者腹会阴联合切除术后会阴切口并发症发生的相关危险因素

探讨高龄直肠癌患者腹会阴联合切除术(APR)后会阴切口并发症发生的相关危险因素。方法采用回顾性病例对照研究的方法,分析中国医学科学院肿瘤医院结直肠外科2007年1月至2018年9月行APR的72例高龄(≥80岁)直肠癌患者的临床病理资料。采用单因素和多因素分析确定影响高龄直肠癌患者APR后会阴切口并发症发生的危险因素。结果72例患者中,男47例,女25例,年龄为(81.8±1.8)岁。术后会阴切口并发症发生率为23.6%(17/72),其中切口感染5例,切口脂肪液化4例,切口延迟愈合8例。所有患者均顺利出院,无围手术期死亡病例。单因素分析显示,术前血清白蛋白<35 g/L、术中置入氟尿嘧啶缓释剂/洛铂冲洗液、盆底修复、糖尿病和冠心病与高龄患者APR术后会阴切口并发症的发生均有关(均P<0.05)。多因素分析显示,未行盆底修复(OR=0.17,95%CI为0.04~0.82;P=0.027)和糖尿病(OR=4.32,95%CI为1.05~17.81;P=0.043)为高龄直肠癌患者APR后会阴切口发生的独立危险因素。结论行APR的高龄直肠癌患者应尽可能保留盆底腹膜,并予以关闭。围手术期血糖监测也是预防会阴切口并发症发生的有力保障。     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

Fungal infections following liver transplantation

With increasing morbidity and mortality from chronic liver disease and acute liver failure, the need for liver transplantation is on the rise. Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions. Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities, a major portion of these patients continue to be affected by post-transplant infections. Of these, fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose. This mini-review aims to discuss the incidence of fungal infections following liver transplantation, the different fungi involved, the risk factors, which predispose these patients to such infections, associated diagnostic challenges, and the role of prophylaxis. The population at risk is increasingly old and frail, suffering from various other co-morbid conditions, and needs special attention. To improve care and to decrease the burden of such infections, we need to identify the at-risk population with more robust clinical and diagnostic parameters. A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.