The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

Synthetic conjugate peptide Fba-Met6 (MP12) induces complement-mediated resistance against disseminated Candida albicans

The fungal genus Candida includes common commensals of the human mucosal membranes, and the most prevalently isolated species, C. albicans, poses a threat of candidemia and disseminated infection associated with an unacceptably high mortality rate and an immense $4 billion burden (US) yearly. Nevertheless, the demand for a vaccine remains wholly unfulfilled and increasingly pressing. We developed a double-peptide construct that is feasible for use in humans with the intention of preventing morbid infection by targeting epitopes derived from fructose bisphosphate aldolase (Fba) and methionine synthase (Met6) which are expressed on the C. albicans cell surface. To test the applicability of the design, we vaccinated mice via the intramuscular (IM) route with the conjugate denoted Fba-Met6 MP12 and showed that the vaccine enhanced survival against a lethal challenge. Because overall endpoint IgG1 and IgG2a antibody titers were robust and these mouse subclasses are associated with protective functionality, we investigated the potential of Fba and Met6 specific antibodies to facilitate the well-defined anti-Candida response by complement, which opsonizes fungi for degradation by primary effectors. Notably, reductions in the fungal burdens and enhanced survival were both abrogated in MP12-vaccinated mice that were pre-challenge dosed with cobra venom factor (CVF), a complement depleting factor. Altogether, we demonstrated that complement is relevant to MP12-based protection against disseminated C. albicans, delineating that a novel, multivalent targeted vaccine against proteins on the surface of C. albicans can enhance the natural response to infection.     

Allergic fungal sinusitis— A clinico-pathological study

The co-existence of fungal elements in allergic nasal Polyposis, has given rise to a distinct clinical entity known as ‘Allergic fungal sinusitis ’ (AF’S). Many a time, these fungal elements may not be diagnosed pre-operatively by routine diagnostic nasal endoscopy or CT scan of paranasal sinuses, due to the florid presentation of nasal polyps, which usually obscure the underlying fungal pathology. The diagnosis is often made intra-operatively. The post-operative confirmation of AFS is by histopathology, fungal smear, fungal culture, allergic murin study and fungal specific IgE titres. We report a series often such cases done in our institution, which highlight that AFS should be considered as a differential diagnosis in Sinonasal Polyposis cases, for their effective management.     

肾移植术后肺部真菌感染的诊治

目的　探讨肾移植术后肺部真菌感染的诊断与治疗。　方法　回顾性分析 4 3例肾移植术后肺部真菌感染患者的临床资料。男 35例 ,女 8例 ,平均年龄 32岁。发病时间平均为术后 5 9d。　结果　 4 3例患者中 ,白色念珠菌 16例 ,克柔念珠菌 4例 ,近平滑念珠菌 2例 ,曲霉菌 4例 ,毛霉菌 3例 ,新型隐球菌 1例 ,奴卡菌 2例 ,其中 14例有细菌、巨细胞病毒混合感染。 11例培养阴性。氟康唑10 0mg/次 ,3次 /d ,连续 10d ,治愈 2 3例 ;两性霉素B脂质体 5 0mg/d ,连续 10d ,治愈 17例 ;死亡 3例。　结论　肺部真菌感染是肾移植术后的严重并发症 ,死亡率高。早期诊断与治疗效果良好。     

Suicide substrate reaction-diffusion equations: Varying the source

The suicide substrate reaction is a model for certain enzyme-inhibitingdrugs. This reaction system is examined assuming that the substratediffuses freely while the enzyme remains fixed. Two sets ofinitial and boundary conditions are examined: one modellingan instantaneous point source, akin to an injection of substrate,the other, a continuous point source, akin to a continuing influx,or intravenous drip, of substrate. The quasi-steady-state assumptionis applied to obtain analytical solutions for a limited parameterspace. Finally, further applications of numerical and analyticalexperimentation on pharmaceutical mechanisms are described.     

多种底物在免疫金银染色检测抗核抗体试验中的联合应用

将多种底物联合应用于免疫金银染色检测ANA试验,与各底物单独应用比较,可明显改善检测的敏感性与核型显示。其中,两种鼠脏器印片联合应用的结果可与Hep-2细胞的结果相当,三种及四种鼠脏器印片联合应用的结果可与Hep-2细胞和一种鼠脏器印片联合应用的结果相当,且均不使正常人ANA阳性率明显升高。     

Non-ulcerative fungal keratitis diagnosed by posterior lamellar biopsy*

We report a case of Fusarium solani keratitis which highlights the difficulties often associated with management of fungal corneal infections. This case demonstrates several unusual and interesting features: the occurrence of deep fungal pathology after superficial injury, the difficulties encountered in attempting to isolate and identify the causative organism, and the protracted course taken by an organism often noted to be rapidly destructive. These features necessitated an individual approach to therapy, employing unconventional medical and surgical techniques to achieve a satisfactory outcome