胰腺囊性肿瘤诊疗及进展

胰腺囊性肿瘤(PCNs)是少见肿瘤，发病原因尚不明确，不良生活习惯（吸烟、饮酒、重咖啡、高脂高蛋白饮食等）、慢性胰腺炎、环境污染因素及遗传因素等是潜在致病因素。PCNs分为浆液性囊性肿瘤（SCN）、黏液性囊性肿瘤（MCN）、胰腺导管内乳头状黏液肿瘤(IPMN)和实性假乳头状瘤（SPN）四种类型。发病症状常不典型，早期诊断难。PCNs具有典型影像特点，单个影像检查技术对PCNs的准确性和局限性不同，CT检查在胰腺病变中仍是最基本、最主要的检查方式。MRI对于小的囊性病灶比CT更有优势。超声内镜（EUS）充分结合了内镜和超声检查的优势，与CT、MRI检查相辅相成，同时还可进行细针穿刺取病理及囊液分析。尽管PCNs大部分为良性，但只要达到切除标准，均应推荐患者进行手术治疗，严格遵循PCNs诊治流程，制订个体化PCNs治疗策略，使患者利益最大化。     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

First-in-human,phase I study of PF-06647263, an anti-EFNA4 calicheamicin antibody–drug conjugate,in patients with advanced solid tumors

PF-06647263, a novel antibody–drug conjugate consisting of an anti-EFNA4 antibody linked to a calicheamicin payload, has shown potent antitumor activity in human xenograft tumor models, including triple-negative breast cancer (TNBC). In the dose-escalation part 1 of this multicenter, open-label, phase I study (NCT02078752), successive cohorts of patients (n, 48) with advanced solid tumors and no available standard therapy received PF-06647263 every 3 weeks (Q3W) or every week (QW), following a modified toxicity probability interval (mTPI) method (initial dosing: 0.015 mg/kg Q3W). Primary objective in part 1 was to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D). In part 2 (dose-expansion cohort), 12 patients with pretreated, metastatic TNBC received PF-06647263 at the RP2D to further evaluate tumor response and overall safety. PF-06647263 QW administration (n, 23) was better tolerated than the Q3W regimen (n, 25) with only 1 DLT reported (thrombocytopenia). The most common AEs with the QW regimen (fatigue, nausea, vomiting, mucosal inflammation, thrombocytopenia, and diarrhea) were mostly mild to moderate in severity. The MTD was not estimated. PF-06647263 exposures increased in a dose-related manner across the doses evaluated. The RP2D was determined to be 0.015 mg/kg QW. Six (10%) patients achieved a confirmed partial response and 22 (36.7%) patients had stable disease. No correlations were observed between tumor responses and EFNA4 expression levels. Study findings showed manageable safety and favorable PK for PF-06647263 administered QW at the RP2D, with preliminary evidence of limited antitumor activity in patients with TNBC and ovarian cancer.     

葫芦素B固体分散体的制备

目的制备葫芦素B固体分散体。方法溶剂法制备固体分散体后,以溶出度为评价指标筛选药物-载体(PVP K30)比例。扫描电子显微镜(SEM)、傅里叶变换红外光谱(FTIR)、差示扫描量热(DSC)、X射线衍射(XRD)进行表征。结果药载比为1∶11时,60 min内溶出度为62.01%。葫芦素B可能以无定形状态分散于载体中。结论该方法简便可行,葫芦素B制成固体分散体后体外溶出度明显提高。     

Molecular insights into hypomineralized enamel

Hypomineralized enamel may be found in connection with the condition molar incisor hypomineralization (MIH), which has a prevalence of around 15% in most parts of the world. Molar incisor hypomineralization is associated with extensive objective and subjective problems, such as hypersensitivity of the affected teeth, enamel breakdown, and problems with retention of restorations. The etiology behind MIH has not yet been elucidated, but a number of possible factors, which affect the same or different functions of ameloblasts during their different stages of maturation, have been suggested. The aim of this study was to utilize multi‐nuclear, solid‐state nuclear magnetic resonance (ss‐NMR) and time‐of‐flight secondary ion mass spectroscopy (ToF‐SIMS) to elucidate any differences, at a molecular level, between enamel powder prepared from normal, healthy teeth and enamel powder prepared from teeth diagnosed with MIH. ³¹P and ²³Na ss‐NMR confirmed the presence of and two different Na⁺ sites in hypomineralized enamel, suggesting a heterogeneous chemical composition. The content of organic components was higher in hypomineralized enamel, as shown by both ¹³C ss‐NMR and ToF‐SIMS, indicating the presence of higher numbers of proteins and phospholipids. The interplay between both is necessary for the formation and mineralization of enamel, which might be disturbed or halted in hypomineralized enamel.     

Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post‐operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%‐53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end‐stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug‐resistant organisms. In this guideline, we describe the epidemiology, clinical presentation, differential diagnosis, potential pathogens, and management. We also provide recommendations for the selection, dosing, and duration of peri‐operative antibiotic prophylaxis to minimize post‐operative SSIs.     

不同氢溴酸右美沙芬口服固体制剂的溶出度考察

目的：对6个厂家不同氢溴酸右美沙芬口服固体制剂进行体外溶出度考察，比较体外溶出情况，为临床用药提供参考。方法：采用转篮法，转速100 r·min^-1，用高效液相色谱法测定氢溴酸右美沙芬口服固体制剂在0.1 mol·L^-1盐酸溶液中的溶出曲线；以威布尔方程拟合溶出参数T₅₀、T_d、m，并对参数进行方差分析。结果：氢溴酸右美沙普通片、分散片、胶囊以及软胶囊的平均累积溶出度分别为94.3%、101.3%、105.2%、93.4%。溶出参数T₅₀、T_d差异较大，其中T₅₀最大的是最小的13.4倍。结论：氢溴酸右美沙片、分散片、胶囊以及软胶囊体外溶出行为差别大，产品质量存在较大差异。     

Hydrogen Transportation Behaviour of V–Ni Solid Solution: A First-Principles Investigation

Hydrogen embrittlement causes deterioration of materials used in metal–hydrogen systems. Alloying is a good option for overcoming this issue. In the present work, first-principles calculations were performed to systematically study the effects of adding Ni on the stability, dissolution, trapping, and diffusion behaviour of interstitial/vacancy H atoms of pure V. The results of lattice dynamics and solution energy analyses showed that the V–Ni solid solutions are dynamically and thermodynamically stable, and adding Ni to pure V can reduce the structural stability of various VH_x phases and enhance their resistance to H embrittlement. H atoms preferentially occupy the characteristic tetrahedral interstitial site (TIS) and the octahedral interstitial site (OIS), which are composed by different metal atoms, and rapidly diffuse along both the energetically favourable TIS → TIS and OIS → OIS paths. The trapping energy of monovacancy H atoms revealed that Ni addition could help minimise the H trapping ability of the vacancies and suppress the retention of H in V. Monovacancy defects block the diffusion of H atoms more than the interstitials, as determined from the calculated H-diffusion barrier energy data, whereas Ni doping contributes negligibly toward improving the H-diffusion coefficient.     

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO,SITO, and AMCLI societies

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain diagnostic procedures, and antiviral intervention forced the panel to use the methods of consensus for shaping some recommendations. Recommendations concerning the two types of transplant were given for the following issues: assessment of pretransplant CMV serostatus, immunological monitoring after transplant, CMV prophylaxis with antivirals, CMV preemptive strategy, and CMV prophylaxis with immunoglobulin infusion and with adoptive immunotherapy. The questions raised by and the recommendations resulting from this consensus conference project may contribute to the improvement of certain crucial aspects of the management of CMV infections in allo‐HSCT and in SOT populations.     

Fungal infections in solid organ transplantation: An update on diagnosis and treatment

Invasive fungal infections constitute an important cause of morbidity and mortality in solid organ transplantation recipients. Since solid organ transplantation is an effective therapy for many patients with end-stage organ failure, prevention and treatment of fungal infections are of vital importance. Diagnosis and management of these infections, however, remain difficult due to the variety of clinical symptoms in addition to the lack of accurate diagnostic methods. The use of fungal biomarkers can lead to an increased diagnostic accuracy, resulting in improved clinical outcomes. The evidence for optimal prophylactic approaches remains inconclusive, which results in considerable variation in the administration of prophylaxis. The implementation of a standard protocol for prophylaxis remains difficult as previous treatment regimens, which can alter the distribution of different pathogens, affect the outcome of antifungal susceptibility testing. Furthermore, the increasing use of antifungals also contributes to incremental costs and the risk of development of drug resistance. This review will highlight risk factors, clinical manifestations and timing of fungal infections and will focus predominately on the current evidence for diagnosis and management of fungal infections.